2-(3-chlorophenyl)acetic acid; 3-chlorophenylacetic acid -Drug Synthesis Database

【结构式】

【分子编号】39705

【品名】2-(3-chlorophenyl)acetic acid; 3-chlorophenylacetic acid

【CA登记号】1878-65-5

【分子式】C₈H₇ClO₂

【分子量】170.59508

【元素组成】C 56.33% H 4.14% Cl 20.78% O 18.76%

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 condensation of labeled 2-(3-chlorphenyl)acetic acid (I) with N-methylethanolamine (II) by means of SOCl2 gives the corresponding amide (III), which is reduced with BH3, yielding the tertiary amine (IV). The reaction of (IV) with PCl3 affords the chloroethylamine (V), which is finally cyclized by means of AlCl3 to provide the target benzazepine.

参考文献中间体

合成目标

【1】 Hieble, J.P.; Wilson III, J.W.; Weinstock, J.; The chemistry and pharmacology of 3-benzazepines derivatives. Drugs Fut 1985, 10, 8, 645.

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)	39705	2-(3-chlorophenyl)acetic acid; 3-chlorophenylacetic acid	1878-65-5	C₈H₇ClO₂	详情	详情
(I)	44628	2-(3-chlorophenyl)acetic acid		C₈H₇ClO₂	详情	详情
(II)	13324	2-Methylaminoethanol; 2-(Methylamino)-1-ethanol	109-83-1	C₃H₉NO	详情	详情
(III)	44044	2-(3-chlorophenyl)-N-(2-hydroxyethyl)-N-methylacetamide		C₁₁H₁₄ClNO₂	详情	详情
(III)	44629	2-(3-chlorophenyl)-N-(2-hydroxyethyl)-N-methylacetamide		C₁₁H₁₄ClNO₂	详情	详情
(IV)	44045	2-[(3-chlorophenethyl)(methyl)amino]-1-ethanol		C₁₁H₁₆ClNO	详情	详情
(IV)	44630	2-[(3-chlorophenethyl)(methyl)amino]-1-ethanol		C₁₁H₁₆ClNO	详情	详情
(V)	44046	2-chloro-N-(3-chlorophenethyl)-N-methyl-1-ethanamine; N-(2-chloroethyl)-N-(3-chlorophenethyl)-N-methylamine		C₁₁H₁₅Cl₂N	详情	详情
(V)	44631	2-chloro-N-(3-chlorophenethyl)-N-methyl-1-ethanamine; N-(2-chloroethyl)-N-(3-chlorophenethyl)-N-methylamine		C₁₁H₁₅Cl₂N	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

Alkylation of 3-chlorophenylacetic acid (I) with allyl bromide (II) using lithium hexamethyldisilazide provided racemic (III), which was resolved by recrystallization of the corresponding diastereoisomeric salts with (S)-alpha-methylbenzylamine. The desired (S)-carboxylic acid (IV) was converted to acid chloride and then treated with methylamine yielding amide (V). Reduction of (V) with LiAlH4 gave amine (VI), which was acylated with benzenesulfonyl chloride to afford sulfonamide (VII). A two-step oxidation of the allyl group of (VII) with osmium tetroxide and N-methylmorpholine N-oxide, followed by sodium periodate cleavage of the resulting diol produced aldehyde (VIII). Reductive condensation of (VIII) with spiro piperidine (IX) using NaBH(OAc)3 furnished adduct (X). Final oxidation of the sulfide group of (X) with one equivalent of Oxone(r) afforded the title sulfoxide.

参考文献中间体

合成目标

【1】 Meurer, L.C.; Oates, B.; Finke, P.E.; et al.; Discovery of potent human CCR5 antagonists for the treatment of HIV-1 infection. 219th ACS Natl Meet (March 26 2000, San Francisco) 2000, Abst MEDI 118.
【2】 Mills, S.G.; MacCoss, M.; Springer, M.S. (Merck & Co., Inc.); Spiro-substd. azacycles as modulators of chemokine receptor activity. US 5962462; WO 9825605 .

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)	39705	2-(3-chlorophenyl)acetic acid; 3-chlorophenylacetic acid	1878-65-5	C₈H₇ClO₂	详情	详情
(II)	11463	3-Bromo-1-propene; 3-Bromopropene；allyl bromide	106-95-6	C₃H₅Br	详情	详情
(III)	39706	2-(3-chlorophenyl)-4-pentenoic acid		C₁₁H₁₁ClO₂	详情	详情
(IV)	39707	(2S)-2-(3-chlorophenyl)-4-pentenoic acid		C₁₁H₁₁ClO₂	详情	详情
(V)	39708	(2S)-2-(3-chlorophenyl)-N-methyl-4-pentenamide		C₁₂H₁₄ClNO	详情	详情
(VI)	39709	N-[(2S)-2-(3-chlorophenyl)-4-pentenyl]-N-methylamine; (2S)-2-(3-chlorophenyl)-N-methyl-4-penten-1-amine		C₁₂H₁₆ClN	详情	详情
(VII)	39710	N-[(2S)-2-(3-chlorophenyl)-4-pentenyl]-N-methylbenzenesulfonamide		C₁₈H₂₀ClNO₂S	详情	详情
(VIII)	39711	N-[(2S)-2-(3-chlorophenyl)-4-oxobutyl]-N-methylbenzenesulfonamide		C₁₇H₁₈ClNO₃S	详情	详情
(IX)	39712			C₁₂H₁₅NS	详情	详情
(X)	39713			C₂₉H₃₃ClN₂O₂S₂	详情	详情

Extended Information