Phenethyl alcohol; 2-phenyl-1-ethanol -Drug Synthesis Database

【结构式】

【分子编号】17897

【品名】Phenethyl alcohol; 2-phenyl-1-ethanol

【CA登记号】60-12-8

【分子式】C₈H₁₀O

【分子量】122.1668

【元素组成】C 78.65% H 8.25% O 13.1%

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)

Reaction between phenetyl alcohol (I) and 3-chloropropionaldehyde diethyl acetal (II) under catalysis of methanesulfonic acid gives the mixed acetal (III), which is then cyclized to the isochromane (IV) by treatment with AlCl3 in nitromethane. Alkylation of 1-(4-fluorophenyl)piperazine (V) with chloride (IV) in the presence of diisopropylethylamine in ethylene glycol yields the title compound, which is converted to the dihydrocloride on treatment with a methanolic solution of hydrogen chloride.

参考文献中间体

合成目标

【1】 TenBrink, R.E.; et al.; (S)-(-)-4-[4-[2-(Isochroman-1-yl)ethyl]-piperazin-1-yl]benzenesulfonamide, a selective dopamine D(4) antagonist. J Med Chem 1996, 39, 13, 2435.
【2】 Ten Brink, R.E.; Ennis, M.D.; Lin, C.-H.; Lahti, R.A.; Romero, A.G.; Sih, J.C. (Pharmacia Corp.); Heterocyclic cpds. for the treatment of CNS and cardiovascular disorders. EP 0737189; JP 1997507224; US 5877317; WO 9518118 .

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)	17897	Phenethyl alcohol; 2-phenyl-1-ethanol	60-12-8	C₈H₁₀O	详情	详情
(II)	17898	3-chloro-1-ethoxypropyl ethyl ether; 3-chloro-1,1-diethoxypropane; 3-Chloropropionaldehyde diethyl acetal	35573-93-4	C₇H₁₅ClO₂	详情	详情
(III)	17899	3-chloro-1-ethoxypropyl phenethyl ether; 1-[2-(3-chloro-1-ethoxypropoxy)ethyl]benzene		C₁₃H₁₉ClO₂	详情	详情
(IV)	17900	1-(2-chloroethyl)-3,4-dihydro-1H-isochromene		C₁₁H₁₃ClO	详情	详情
(V)	12143	1-(4-Fluorophenyl)piperazine	2252-63-3	C₁₀H₁₃FN₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

A synthesis of the R-(+) isomer has also been reported: Reaction of phenethyl alcohol (I) and ethyl 3,3-diethoxypropionate (VI) in the presence of titanium tetrachloride affords the isochromane (VII), which is hydrolyzed to acid (VIII) with NaOH in aqueous ethanol. Resolution of the racemic acid (VIII) is effected by conversion into the diastereomeric salt with R-(+)-a-methylbenzylamine (IX) which, after recrystallization from dichloromethane and ethyl acetate, is liberated by treatment with hydrochloric acid, to yield the R-(-) acid (X). This acid is reduced to alcohol (XI) with borane-dimethyl sulfide in tetrahydrofuran. Treatment of XI with methanesulfonyl chloride, diisopropylethylamine, and a trace of dimethylaminopyridine (DMAP) in tetrahydrofuran affords mesylate (XII), which is subsequently treated with piperazine (V) in ethylene glycol to afford the R-(+) compound, isolated as the methanesulfonate salt.

参考文献中间体

合成目标

【1】 TenBrink, R.E.; et al.; (S)-(-)-4-[4-[2-(Isochroman-1-yl)ethyl]-piperazin-1-yl]benzenesulfonamide, a selective dopamine D(4) antagonist. J Med Chem 1996, 39, 13, 2435.
【2】 Ten Brink, R.E.; Ennis, M.D.; Lin, C.-H.; Lahti, R.A.; Romero, A.G.; Sih, J.C. (Pharmacia Corp.); Heterocyclic cpds. for the treatment of CNS and cardiovascular disorders. EP 0737189; JP 1997507224; US 5877317; WO 9518118 .

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)	17897	Phenethyl alcohol; 2-phenyl-1-ethanol	60-12-8	C₈H₁₀O	详情	详情
(V)	12143	1-(4-Fluorophenyl)piperazine	2252-63-3	C₁₀H₁₃FN₂	详情	详情
(VI)	17901	Ethyl 3,3-diethoxypropanoate	10601-80-6	C₉H₁₈O₄	详情	详情
(VII)	17902	ethyl 2-(3,4-dihydro-1H-isochromen-1-yl)acetate		C₁₃H₁₆O₃	详情	详情
(VIII)	17903	2-(3,4-dihydro-1H-isochromen-1-yl)acetic acid		C₁₁H₁₂O₃	详情	详情
(IX)	20042	(1S)-1-phenyl-1-ethanamine; (1S)-1-phenylethylamine		C₈H₁₁N	详情	详情
(X)	17905	2-[(1R)-3,4-dihydro-1H-isochromen-1-yl]acetic acid		C₁₁H₁₂O₃	详情	详情
(XI)	17906	2-[(1R)-3,4-dihydro-1H-isochromen-1-yl]-1-ethanol		C₁₁H₁₄O₂	详情	详情
(XII)	17907	2-[(1R)-3,4-dihydro-1H-isochromen-1-yl]ethyl methanesulfonate		C₁₂H₁₆O₄S	详情	详情

Extended Information