1-(4-methoxyphenyl)-2-phenyl-1-ethanone -Drug Synthesis Database

【结构式】

【分子编号】30343

【品名】1-(4-methoxyphenyl)-2-phenyl-1-ethanone

【CA登记号】

【分子式】C₁₅H₁₄O₂

【分子量】226.27496

【元素组成】C 79.62% H 6.24% O 14.14%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(I)

The reaction of 1-(4-methoxyphenyl)-2-phenylethan-1-one (I) with ethyl bromide (A) gave (II) in nearly quantitative yield. Demethoxylation of (II) with pyridine hydrochloride gave (III) in about 70% yield. Treatment of (III) with dimethylaminoethyl chloride (B) gave (IV) in more than 60% yield. Reaction of (IV) with 3'-(2-tetrahydropyranyloxy)phenylmagnesium bromide (C) gave (V) in about 60% yield. Refluxing a solution of (V) in ethanolic hydrochloric acid gave the stereoisomeric E- and Z-mixture (VIa, VIb) of the hydrochloric salt. Fractional crystallization of the mixture in methanol/ether yielded the pure hydrochloric salt of the E-isomer in 48% yield. Conversion of the hydrochloric salt into the free base and treatment of the latter with citric acid yielded the appropriate K-21060E citrate.

参考文献中间体

合成目标

【1】 Schickaneder, H.; Loser, R.; Grill, H. (Klinge Pharma GmbH); 1,1,2-triphenylbut-1-ene derivatives. DE 3046719; EP 0054168; US 5047431 .
【2】 Loser, R.; Seibel, K.; Janiak, P.-St.; K-21060 E. Drugs Fut 1984, 9, 3, 186.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(B)	11907	Dimethylaminoethyl chloride; 2-Dimethylaminoethyl chloride; 2-Chloro-N,N-dimethyl-1-ethanamine; N-(2-Chloroethyl)-N,N-dimethylamine	107-99-3	C₄H₁₀ClN	详情	详情
(A)	30344	1-bromoethane；ethyl bromide	74-96-4	C₂H₅Br	详情	详情
(VIa)	30350	3-((E)-1-[4-[2-(dimethylamino)ethoxy]phenyl]-2-phenyl-1-butenyl)phenol		C₂₆H₂₉NO₂	详情	详情
(VIb)	30351	3-((Z)-1-[4-[2-(dimethylamino)ethoxy]phenyl]-2-phenyl-1-butenyl)phenol		C₂₆H₂₉NO₂	详情	详情
(I)	30343	1-(4-methoxyphenyl)-2-phenyl-1-ethanone		C₁₅H₁₄O₂	详情	详情
(II)	30345	1-(4-methoxyphenyl)-2-phenyl-1-butanone		C₁₇H₁₈O₂	详情	详情
(III)	30346	1-(4-hydroxyphenyl)-2-phenyl-1-butanone		C₁₆H₁₆O₂	详情	详情
(IV)	30347	1-[4-[2-(dimethylamino)ethoxy]phenyl]-2-phenyl-1-butanone	68047-07-4	C₂₀H₂₅NO₂	详情	详情
(V)	30349	1-[4-[2-(dimethylamino)ethoxy]phenyl]-2-phenyl-1-[3-(tetrahydro-2H-pyran-2-yloxy)phenyl]-1-butanol		C₃₁H₃₉NO₄	详情	详情
(C)	30348	bromo[3-(tetrahydro-2H-pyran-2-yloxy)phenyl]magnesium		C₁₁H₁₃BrMgO₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XXI)

Condensation of desoxybenzoin (I) with 2-(tetra-hydropyranyloxy)ethyl bromide (XIV) by means of aqueous NaOH and TEBAC as before gives 1,2-diphenyl-4-(tetrahydropyranyloxy)-1-butanone (XV), which by a Grignard condensation with 4-methoxyphenylmagnesium bromide (XVI) -prepared from 4-bromoanisole (XVII) and Mg in THF- provides the triphenylbutanol derivative (XVIII). Cleavage of the THP-protecting group of compound (XVIII) with H2SO4 in ethanol/water at room temperature affords the butane-1,4-diol derivative (XIX), which is cyclized by means of H2SO4 in hot ethanol/ water to yield 2-(4-methoxyphenyl)-2,3-diphenyltetrahydrofuran (XX). Finally, this compound is treated with 48% HBr in refluxing AcOH to give 4-(4-hydroxyphenyl)-3,4-diphenyl-3-buten-1-ol (X) as a (Z):(E)-isomeric mixture, from which the desired (Z)-isomer is separated by chemical work up.

参考文献中间体

合成目标

【1】 Sorbera, L.A.; Castaner, J.; Bayes, M.; Ospemifene. Drugs Fut 2004, 29, 1, 38.
【2】 Toivola, R.J.; Karjalainen, A.J.; Kurkela, K.O.A.; Soderwall, M.-L.; Kangas, L.V.M.; Blanco, G.L.; Sundquist, H.K. (Orion Corporation); Tri-phenyl alkene derivs. and their oestrogenic, anti-oestrogenic and progestanic uses. US 4996225; US 5491173 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	41003	1,2-diphenyl-1-ethanone; Deoxybenzoin-2-phenylacetophenone; Dexybenzoin	451-40-1	C₁₄H₁₂O	详情	详情
(X)	52025	4-[(Z)-4-hydroxy-1,2-diphenyl-1-butenyl]phenol		C₂₂H₂₀O₂	详情	详情
(XIV)	26934	2-bromoethyl tetrahydro-2H-pyran-2-yl ether		C₇H₁₃BrO₂	详情	详情
(XV)	52021	1,2-diphenyl-4-(tetrahydro-2H-pyran-2-yloxy)-1-butanone		C₂₁H₂₄O₃	详情	详情
(XVI)	37674	Bromo(4-methoxyphenyl)magnesium; 4-Methoxyphenylmagnesium bromide	352-13-6	C₇H₇BrMgO	详情	详情
(XVII)	63436	1-bromo-4-methoxybenzene; 4-bromophenyl methyl ether		C₇H₇BrO	详情	详情
(XVIII)	52022	1-(4-methoxyphenyl)-1,2-diphenyl-4-(tetrahydro-2H-pyran-2-yloxy)-1-butanol		C₂₈H₃₂O₄	详情	详情
(XIX)	52023	1-(4-methoxyphenyl)-1,2-diphenyl-1,4-butanediol		C₂₃H₂₄O₃	详情	详情
(XX)	52024	2-(4-methoxyphenyl)-2,3-diphenyltetrahydrofuran; 4-(2,3-diphenyltetrahydro-2-furanyl)phenyl methyl ether		C₂₃H₂₂O₂	详情	详情
(XXI)	30343	1-(4-methoxyphenyl)-2-phenyl-1-ethanone		C₁₅H₁₄O₂	详情	详情
(XXII)	63437	1-(4-methoxyphenyl)-2-phenyl-4-(tetrahydro-2H-pyran-2-yloxy)-1-butanone		C₂₂H₂₆O₄	详情	详情
(XXIII)	17616	bromo(phenyl)magnesium; Phenyl Magnesium Bromide	100-58-3	C₆H₅BrMg	详情	详情

Extended Information