JPH0739379B2 - Process for producing trans-1,1,2-triphenyl-but-1-ene derivative - Google Patents
Process for producing trans-1,1,2-triphenyl-but-1-ene derivativeInfo
- Publication number
- JPH0739379B2 JPH0739379B2 JP63332691A JP33269188A JPH0739379B2 JP H0739379 B2 JPH0739379 B2 JP H0739379B2 JP 63332691 A JP63332691 A JP 63332691A JP 33269188 A JP33269188 A JP 33269188A JP H0739379 B2 JPH0739379 B2 JP H0739379B2
- Authority
- JP
- Japan
- Prior art keywords
- trans
- parts
- phenyl
- general formula
- triphenyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 238000000034 method Methods 0.000 title claims description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 16
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 12
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 12
- 239000003960 organic solvent Substances 0.000 claims description 7
- 239000007795 chemical reaction product Substances 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 5
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- 238000004128 high performance liquid chromatography Methods 0.000 description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 229910021529 ammonia Inorganic materials 0.000 description 5
- 239000013078 crystal Substances 0.000 description 5
- 238000002844 melting Methods 0.000 description 5
- 230000008018 melting Effects 0.000 description 5
- 239000012044 organic layer Substances 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- ZVQOOHYFBIDMTQ-UHFFFAOYSA-N [methyl(oxido){1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}-lambda(6)-sulfanylidene]cyanamide Chemical compound N#CN=S(C)(=O)C(C)C1=CC=C(C(F)(F)F)N=C1 ZVQOOHYFBIDMTQ-UHFFFAOYSA-N 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- DYLIWHYUXAJDOJ-OWOJBTEDSA-N (e)-4-(6-aminopurin-9-yl)but-2-en-1-ol Chemical compound NC1=NC=NC2=C1N=CN2C\C=C\CO DYLIWHYUXAJDOJ-OWOJBTEDSA-N 0.000 description 2
- JQKMNNYZQUQIJJ-UHFFFAOYSA-N 1,1-diphenylbut-1-en-2-ylbenzene Chemical class C=1C=CC=CC=1C(CC)=C(C=1C=CC=CC=1)C1=CC=CC=C1 JQKMNNYZQUQIJJ-UHFFFAOYSA-N 0.000 description 2
- BUKANFTWZXJIGD-UHFFFAOYSA-N 3-[1-[4-[2-(dimethylamino)ethoxy]phenyl]-1-hydroxy-2-phenylbutyl]phenol Chemical compound C=1C=C(OCCN(C)C)C=CC=1C(O)(C=1C=C(O)C=CC=1)C(CC)C1=CC=CC=C1 BUKANFTWZXJIGD-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 229940046836 anti-estrogen Drugs 0.000 description 2
- 230000001833 anti-estrogenic effect Effects 0.000 description 2
- 239000000328 estrogen antagonist Substances 0.000 description 2
- 239000012452 mother liquor Substances 0.000 description 2
- 229960001603 tamoxifen Drugs 0.000 description 2
- HMUNWXXNJPVALC-UHFFFAOYSA-N 1-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]-2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical group C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)C(CN1CC2=C(CC1)NN=N2)=O HMUNWXXNJPVALC-UHFFFAOYSA-N 0.000 description 1
- VFFBJZCCXOYRNN-UHFFFAOYSA-N 1-[4-[2-(dimethylamino)ethoxy]phenyl]-1,2-diphenylbutan-1-ol Chemical compound C=1C=CC=CC=1C(O)(C=1C=CC(OCCN(C)C)=CC=1)C(CC)C1=CC=CC=C1 VFFBJZCCXOYRNN-UHFFFAOYSA-N 0.000 description 1
- FKDKAGHZAOFATR-UHFFFAOYSA-N 1-phenylbut-1-enylbenzene Chemical compound C=1C=CC=CC=1C(=CCC)C1=CC=CC=C1 FKDKAGHZAOFATR-UHFFFAOYSA-N 0.000 description 1
- VZSRBBMJRBPUNF-UHFFFAOYSA-N 2-(2,3-dihydro-1H-inden-2-ylamino)-N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]pyrimidine-5-carboxamide Chemical group C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C(=O)NCCC(N1CC2=C(CC1)NN=N2)=O VZSRBBMJRBPUNF-UHFFFAOYSA-N 0.000 description 1
- WZFUQSJFWNHZHM-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical group C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)CC(=O)N1CC2=C(CC1)NN=N2 WZFUQSJFWNHZHM-UHFFFAOYSA-N 0.000 description 1
- MPMAKJDYHJDJDO-UHFFFAOYSA-N 3-[1-[4-[2-(diethylamino)ethoxy]phenyl]-1-hydroxy-2-phenylbutyl]phenol Chemical compound C=1C=C(OCCN(CC)CC)C=CC=1C(O)(C=1C=C(O)C=CC=1)C(CC)C1=CC=CC=C1 MPMAKJDYHJDJDO-UHFFFAOYSA-N 0.000 description 1
- CONKBQPVFMXDOV-QHCPKHFHSA-N 6-[(5S)-5-[[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]methyl]-2-oxo-1,3-oxazolidin-3-yl]-3H-1,3-benzoxazol-2-one Chemical group C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)C[C@H]1CN(C(O1)=O)C1=CC2=C(NC(O2)=O)C=C1 CONKBQPVFMXDOV-QHCPKHFHSA-N 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 101000652359 Homo sapiens Spermatogenesis-associated protein 2 Proteins 0.000 description 1
- 101000642464 Homo sapiens Spermatogenesis-associated protein 2-like protein Proteins 0.000 description 1
- 102100030254 Spermatogenesis-associated protein 2 Human genes 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- -1 carbinol compound Chemical class 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 239000000262 estrogen Substances 0.000 description 1
- 238000010575 fractional recrystallization Methods 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 238000006317 isomerization reaction Methods 0.000 description 1
- IFWCCHXFUMLVAF-WEZQJLTASA-N n-[(4r,4as,7ar,12br)-9-hydroxy-3-methyl-7-oxo-2,4,5,6,7a,13-hexahydro-1h-4,12-methanobenzofuro[3,2-e]isoquinoline-4a-yl]-2-sulfanylacetamide Chemical compound O([C@H]1C(CC[C@]23NC(=O)CS)=O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O IFWCCHXFUMLVAF-WEZQJLTASA-N 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/52—Improvements relating to the production of bulk chemicals using catalysts, e.g. selective catalysts
Landscapes
- Catalysts (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Description
【発明の詳細な説明】 ［産業上の利用分野］ この発明は、トランス−1,1,2−トリフェニル−ブト−
１−エン誘導体の製造法に関するものである。DETAILED DESCRIPTION OF THE INVENTION [Industrial field of application] The present invention relates to trans-1,1,2-triphenyl-but-
The present invention relates to a method for producing a 1-ene derivative.
［従来の技術］ 近年、抗エストロゲン特性をもつためホルモン依存性乳
房腫瘍の処置に適当な一連のトリフェニルブテン誘導体
が報告されてきた（R.スザーランドおよびV.C.ジョルダ
ン「非ステロイド抗エストロゲン（Nonsteroidal Anti
oestrogens）」アカデミック・プレス1981年）。PRIOR ART Recently, a series of triphenylbutene derivatives suitable for the treatment of hormone-dependent breast tumors due to their anti-estrogen properties have been reported (R. Sutherland and VC Jordan “Nonsteroidal Anti-Estrogens”).
oestrogens) "Academic Press 1981).
活性成分１−［４′−（２−ジメチルアミノエトキシ）
フェニル］−トランス−1,2−ジフェニル−ブト−１−
エンは、治療に用いられ、同時にタモキシフェン（TAMO
XIFEN）（INN）という名称で世界的に知られるようにな
った。Active ingredient 1- [4 '-(2-dimethylaminoethoxy)
Phenyl] -trans-1,2-diphenyl-but-1-
En is used for treatment and at the same time tamoxifen (TAMO
It became known worldwide under the name XIFEN) (INN).
1,1,2−トリフェニル−ブト−１−エン誘導体の合成時
において、一般式２のジアステレオマー性カルビノール
の脱水段階で一般式３および１の幾何学的異性体オレフ
ィン「シス／トランスーまたはE/Z体］が混合状態で蓄
積する。During the synthesis of the 1,1,2-triphenyl-but-1-ene derivative, the diastereomeric carbinol of the general formula 2 is dehydrated at the geometric isomer olefins of the general formulas 3 and 1 "cis / trans- Or E / Z body] accumulates in a mixed state.
活性異性体の１つだけが臨床適応されるため、生成する
異性体混合物から純トランス体を単離する必要があっ
た。これは、例えば分別再結晶化またはクロマトグラフ
ィーのような大きな損失と費用のかかる方法によってし
かいままでなされていなかった。［イギリス国特許番号
1013907号；アメリカ特許番号4,536,516号；ヨーロッパ
特許番号0054168号;G.R.ベッドフォードおよびD.N.リチ
ャードソン、ネイチャー（Nature）、212巻、733−734
頁（1966年）;P.ソハーら、アクタ・チミカ・アカデミ
カ・サイエンスチカ・ハンガリア（Acta Chim.Acad.Sc
i.Hung.）、100巻69−74頁（1979年）;D.W.ロバートソ
ンおよびJ.A.カツェンエレンボーゲン、ジャーナル・オ
ブ・オーガニック・ケミストリー（J.Org.Chem.）、47
巻、2387−2393頁（1982年）;P.C.ルエニッツら、ジャ
ーナル・オブ・メディシナル・ケミストリー（J.Med.Ch
em.）、25巻、1056−1060頁;R.D.アームストロング、ジ
ャーナル・オブ・クロマトグラフィー（J.Chromatog
r.）、414巻192−196頁（1987年）］。 Since only one of the active isomers was clinically indicated, it was necessary to isolate the pure trans form from the resulting isomer mixture. This has hitherto been done only by large loss and costly methods such as fractional recrystallization or chromatography. [UK patent number
1013907; U.S. Patent No. 4,536,516; European Patent No. 0054168; GR Bedford and DN Richardson, Nature, Volume 212, 733-734.
Page (1966); P. Soher et al., Acta Chim.Acad.Sc
i.Hung.) 100, 69-74 (1979); DW Robertson and JA Katzen Ellenbogen, Journal of Organic Chemistry (J.Org.Chem.), 47.
Volume, 2387-2393 (1982); PC Luenitz et al., Journal of Medicinal Chemistry (J.Med.Ch.
em.), 25, 1056-1060; RD Armstrong, Journal of Chromatography (J. Chromatog
r.), 414, pp. 192-196 (1987)].
シス体が優勢な従来無価値の母液分画をトランス体に変
換することが可能になってはじめてタモキシフェンの収
率を増加させることができる。ヨーロッパ特許番号0127
128号に見られるように、シス体は上昇した温度で強塩
酸条件下でトランス体に変換することができる。The yield of tamoxifen can be increased only when it is possible to convert the conventionally worthless mother liquor fraction in which the cis form is predominant into the trans form. European Patent No. 0127
As seen in No. 128, the cis form can be converted to the trans form at elevated temperature under strong hydrochloric acid conditions.
驚くべきことに、一般式１のトランス−1,1,2−トリフ
ェニル−ブト−１−エン誘導体の製造方法における実質
的な単純化が可能になった。後に示すとおり、一般式２
を有するカルビノール化合物は、一定条件下で一般式１
を有するトランス−オレフィンに１工程で大部分変換さ
れる。それによって従来の製造方法で必要であった工
程、 ａ）ジアステレオマー性カルビノールの脱水後のシス／
トランス異性体混合物の単離、 ｂ）結晶化またはクロマトグラフィーによるトランス体
の分離および ｃ）シス体が多い母液分画の再異性化 が省略することができる。Surprisingly, a substantial simplification in the process for preparing the trans-1,1,2-triphenyl-but-1-ene derivative of the general formula 1 has become possible. As shown below, the general formula 2
A carbinol compound having the general formula 1
Are mostly converted in one step to trans-olefins having Thereby, the steps required in the conventional production method, a) cis / after dehydration of diastereomeric carbinol
Isolation of the trans isomer mixture, b) separation of the trans isomer by crystallization or chromatography and c) re-isomerization of the cis-rich mother liquor fraction can be omitted.
本発明による方法では、一般式２のカルビノールは有機
溶媒の不存在下で、上昇した温度で塩酸または硫酸の影
響下に一般式１のトランス−オレフィンに直接変換す
る。これらの条件下で一般式３のシス−オレフィンの生
成は実質的に抑制される。In the process according to the invention, carbinols of the general formula 2 are converted directly into the trans-olefins of the general formula 1 in the absence of organic solvents at elevated temperature under the influence of hydrochloric acid or sulfuric acid. Under these conditions, the production of cis-olefin of general formula 3 is substantially suppressed.
一般式２によるカルビノールの一般式１のトランス−オ
レフィンへの変換は、好ましくは50−60℃の温度範囲で
実施される。塩酸または硫酸は上昇した温度で好ましく
は12−16時間、少なくとも10時間作用させる。The conversion of carbinol to the trans-olefin of general formula 1 according to general formula 2 is preferably carried out in the temperature range of 50-60 ° C. Hydrochloric acid or sulfuric acid is allowed to act at elevated temperature for preferably 12-16 hours, at least 10 hours.
本発明を以下に述べる具体的な実施例に基づいてさらに
詳しく説明する。The present invention will be described in more detail based on the specific examples described below.
実施例１ １−［４′−（２−ジメチルアミノエトキシ）フェニ
ル］−1,2−ジフェニル−ブタン−１−オールの１部を5
0容量％硫酸10部中で攪拌し、懸濁液を激しく攪拌しな
がら14時間55℃に加熱した。続いて冷却し2.5部の氷と
濃アンモニア12.5部を加えアルカリ性とした。反応生成
物を酢酸エチルで抽出し、有機層を水で繰り返し洗浄し
た。真空下で有機溶媒を除去した後、１−［４′−（２
−ジメチルアミノエトキシ）フェニル］−トランス−1,
2−ジフェニル−ブト−１−エン94％［HPLC］の0.9部の
残渣が得られた。アセトンからの結晶は融点90℃であ
る。含量:99.4％［HPLC］。Example 1 1 part of 1- [4 '-(2-dimethylaminoethoxy) phenyl] -1,2-diphenyl-butan-1-ol was added to 5 parts.
The mixture was stirred in 10 parts of 0% by volume sulfuric acid and the suspension was heated to 55 ° C. for 14 hours with vigorous stirring. Subsequently, the mixture was cooled and made alkaline with 2.5 parts of ice and 12.5 parts of concentrated ammonia. The reaction product was extracted with ethyl acetate, and the organic layer was repeatedly washed with water. After removing the organic solvent under vacuum, 1- [4 '-(2
-Dimethylaminoethoxy) phenyl] -trans-1,
A residue of 0.9 parts of 2-diphenyl-but-1-ene 94% [HPLC] was obtained. Crystals from acetone have a melting point of 90 ° C. Content: 99.4% [HPLC].
実施例２ １−［４′−（２−ジメチルマミノエトキシ）フェニ
ル］−1,2−ジフェニル−ブタン−１−オールの１部を3
2重量％の塩酸６部中で攪拌し、懸濁液を激しく攪拌し
ながら16時間52℃に加熱した。続いて冷却し２部の氷と
濃アンモニア６部を加えアルカリ化した。反応生成物を
酢酸エチルで抽出し、有機層を水で繰り返し洗浄した。
真空下で有機溶媒を除去した後、１−［４′−（２−ジ
メチルアミノエトキシ）フェニル］−トランス−1,2−
ジフェニル−ブト−１−エン96％［HPLC］の0.97部の残
渣が得られた。メタノール／水からの結晶は融点96から
98℃である。含量:99.7％［HPLC］。Example 2 1 part of 1- [4 '-(2-dimethylmaminoethoxy) phenyl] -1,2-diphenyl-butan-1-ol was added to 3 parts.
It was stirred in 6 parts of 2% by weight hydrochloric acid and the suspension was heated to 52 ° C. for 16 hours with vigorous stirring. Subsequently, it was cooled and alkalized by adding 2 parts of ice and 6 parts of concentrated ammonia. The reaction product was extracted with ethyl acetate, and the organic layer was repeatedly washed with water.
After removing the organic solvent under vacuum, 1- [4 '-(2-dimethylaminoethoxy) phenyl] -trans-1,2-
A residue of 0.97 parts of diphenyl-but-1-ene 96% [HPLC] was obtained. Crystals from methanol / water have a melting point of 96
98 ° C. Content: 99.7% [HPLC].
実施例３ １−［４′−（２−ジメチルアミノエトキシ）フェニ
ル］−１−（３′−ヒドロキシフェニル）−２−フェニ
ル−ブタン−１−オールの１部を50容量％の硫酸９部中
で攪拌し、懸濁液を激しく攪拌しながら15時間52℃に加
熱した。続いて冷却し３部の氷と濃アンモニア12部を加
えアルカリ化した。反応生成物をジクロロメタンで抽出
し、有機層を水で繰り返し洗浄した。真空下で有機溶媒
を除去した後、１−［４′−（２−ジメチルアミノエト
キシ）フェニル］−トランス−１−（３′−ヒドロキシ
フェニル）−２−フェニル−ブト−１−エン90％［HPL
C］の0.9部の残渣が得られた。エタノールからの結晶は
融点164℃である。含量:99.5％［HPLC］。Example 3 1 part of 1- [4 '-(2-dimethylaminoethoxy) phenyl] -1- (3'-hydroxyphenyl) -2-phenyl-butan-1-ol in 9 parts of 50% by volume sulfuric acid. The suspension was heated to 52 ° C. for 15 hours with vigorous stirring. Subsequently, it was cooled and alkalized by adding 3 parts of ice and 12 parts of concentrated ammonia. The reaction product was extracted with dichloromethane, and the organic layer was repeatedly washed with water. After removing the organic solvent under vacuum, 1- [4 '-(2-dimethylaminoethoxy) phenyl] -trans-1- (3'-hydroxyphenyl) -2-phenyl-but-1-ene 90% [ HPL
C] of 0.9 part of residue was obtained. Crystals from ethanol have a melting point of 164 ° C. Content: 99.5% [HPLC].
実施例４ １−［４′−（２−ジメチルアミノエトキシ）フェニ
ル］−１−（３′ヒドロキシフェニル）−２−フェニル
−ブタン−１−オールの１部を37重量％の塩酸６部中で
攪拌し、懸濁液を激しく攪拌しながら16時間50℃に加熱
した。続いて冷却し３部の氷と濃アンモニア４部を加え
アルカリ化した。反応生成物をジクロロメタンで抽出
し、有機層を水で繰り返し洗浄した。真空下で有機溶媒
を除去した後、１−［４′−（２−ジメチルアミノエト
キシ）フェニル］−トランス−１−（３′−ヒドロキシ
フェニル）−２−フェニル−ブト−１−エン93％［HPL
C］の0.85部の残渣が得られた。エタノールからの結晶
は融点164℃である。含量:99.6％［HPLC］。Example 4 1 part of 1- [4 '-(2-dimethylaminoethoxy) phenyl] -1- (3'hydroxyphenyl) -2-phenyl-butan-1-ol in 6 parts of 37% by weight hydrochloric acid. Upon stirring, the suspension was heated to 50 ° C. for 16 hours with vigorous stirring. Subsequently, it was cooled and alkalized by adding 3 parts of ice and 4 parts of concentrated ammonia. The reaction product was extracted with dichloromethane, and the organic layer was repeatedly washed with water. After removing the organic solvent under vacuum, 1- [4 '-(2-dimethylaminoethoxy) phenyl] -trans-1- (3'-hydroxyphenyl) -2-phenyl-but-1-ene 93% [ HPL
C] of 0.85 parts of residue was obtained. Crystals from ethanol have a melting point of 164 ° C. Content: 99.6% [HPLC].
実施例５ １−［４′−（２−ジエチルアミノエトキシ）フェニ
ル］−１−（３′−ヒドロキシフェニル）−２−フェニ
ル−ブタン−１−オールの１部を37重量％の塩酸８部中
で攪拌し、懸濁液を激しく攪拌しながら15時間52℃に加
熱した。続いて冷却し４部の氷と濃アンモニア５部を加
えアルカリ化した。反応生成物をジクロロメタンで抽出
し、有機層を水で繰り返し洗浄した。真空下で有機溶媒
を除去した後、１−［４′−（２−ジエチルアミノエト
キシ）フェニル］−トランス−１−（３′−ヒドロキシ
フェニル）−２−フェニル−ブト−１−エン95％［HPL
C］の0.95部の残渣が得られた。イソプロパノールから
の結晶は融点130℃である。含量:99.5％［HPLC］。Example 5 1 part of 1- [4 '-(2-diethylaminoethoxy) phenyl] -1- (3'-hydroxyphenyl) -2-phenyl-butan-1-ol in 8 parts of 37% by weight hydrochloric acid. Upon stirring, the suspension was heated to 52 ° C. for 15 hours with vigorous stirring. Subsequently, it was cooled and alkalized by adding 4 parts of ice and 5 parts of concentrated ammonia. The reaction product was extracted with dichloromethane, and the organic layer was repeatedly washed with water. After removing the organic solvent under vacuum, 1- [4 '-(2-diethylaminoethoxy) phenyl] -trans-1- (3'-hydroxyphenyl) -2-phenyl-but-1-ene 95% [HPL
C], 0.95 parts of residue was obtained. Crystals from isopropanol have a melting point of 130 ° C. Content: 99.5% [HPLC].
Claims (2)
は硫酸媒質中で加熱し、反応生成物を常法で処理するこ
とからなる、 一般式、 ［式中、R1はCH3、CH2CH3およびR2はＨ、OHである、］ を有するトランス−1,1,2−トリフェニル−ブト−１−
エン誘導体の製造方法。1. A general formula, [Wherein R 1 and R 2 are as defined in the general formula 1] Carbinol is heated in a strong hydrochloric acid or sulfuric acid medium excluding an organic solvent, and the reaction product is treated in a conventional manner. , The general formula, [Wherein R 1 is CH 3 , CH 2 CH 3 and R 2 is H, OH] having the formula trans-1,1,2-triphenyl-but-1-
Method for producing ene derivative.
32から37重量％で、硫酸濃度が少なくとも40重量％好ま
しくは45から50容量％の範囲内である請求項１記載の方
法。2. A hydrochloric acid concentration of at least 25% by weight, preferably
A process according to claim 1, wherein the sulfuric acid concentration is in the range of at least 40% by weight, preferably 45 to 50% by volume, at 32 to 37% by weight.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP63332691A JPH0739379B2 (en) | 1988-12-28 | 1988-12-28 | Process for producing trans-1,1,2-triphenyl-but-1-ene derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP63332691A JPH0739379B2 (en) | 1988-12-28 | 1988-12-28 | Process for producing trans-1,1,2-triphenyl-but-1-ene derivative |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH02184659A JPH02184659A (en) | 1990-07-19 |
| JPH0739379B2 true JPH0739379B2 (en) | 1995-05-01 |
Family
ID=18257803
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP63332691A Expired - Lifetime JPH0739379B2 (en) | 1988-12-28 | 1988-12-28 | Process for producing trans-1,1,2-triphenyl-but-1-ene derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0739379B2 (en) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP4572407B2 (en) * | 2005-03-04 | 2010-11-04 | 学校法人東京理科大学 | Method for producing droloxifene |
| JP4940429B2 (en) * | 2006-09-19 | 2012-05-30 | 国立大学法人 岡山大学 | Method for producing triarylethylethene derivative |
| WO2019196812A1 (en) * | 2018-04-09 | 2019-10-17 | 上海科技大学 | Protein degradation targeting compound, anti-tumor application, intermediate thereof and use of intermediate |
| CN111606883B (en) | 2019-02-25 | 2023-05-09 | 上海科技大学 | Sulfur-containing compound based on glutarimide skeleton and application thereof |
| WO2021023233A1 (en) | 2019-08-05 | 2021-02-11 | 上海科技大学 | Egfr protein degradant and anti-tumor application thereof |
-
1988
- 1988-12-28 JP JP63332691A patent/JPH0739379B2/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| JPH02184659A (en) | 1990-07-19 |
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