(4S)-4-benzyl-3-[(E)-3-(3-fluorophenyl)-2-propenoyl]-1,3-oxazolidin-2-one -Drug Synthesis Database

【结构式】

【分子编号】63983

【品名】(4S)-4-benzyl-3-[(E)-3-(3-fluorophenyl)-2-propenoyl]-1,3-oxazolidin-2-one

【CA登记号】

【分子式】C₁₉H₁₆FNO₃

【分子量】325.3393832

【元素组成】C 70.14% H 4.96% F 5.84% N 4.31% O 14.75%

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：(III)

m-Fluorocinnamic acid (I) is coupled to (S)-4-benzyloxazolidin-2-one (II), via the corresponding mixed anhydride with pivaloyl chloride, to furnish the N-cinnamoyl oxazolidinone (III). Cycloaddition of (III) with N-methoxymethyl-N-trimethylsilylmethyl benzylamine (IV) in the presence of trifluoroacetic acid produces a mixture of the diastereoisomeric pyrrolidines (V) and (VI), separable by column chromatography. The desired isomer (V) is then reduced by means of LiAlH4 to the primary alcohol (VII), which is further protected by silylation with t-butyldimethylsilyl chloride. The resultant silyl ether (VIII) is then subjected to benzyl group cleavage under transfer hydrogenation conditions, producing pyrrolidine (IX) (1).

参考文献中间体

合成目标

【1】 Mills, S.G.; Kim, D.; Hale, J.; MacCoss, M.; Berk, S.; Chapman, K.; Lynch, C.; Caldwell, C.; Willoughby, C.; Rosauer, K. (Merck & Co., Inc.); Pyrrolidine modulators of chemokine receptor activity. US 6265434; WO 0059503 .

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)	63980	m-Fluorocinnamic acid; (E)-3-(3-fluorophenyl)-2-propenoic acid		C₉H₇FO₂	详情	详情
(II)	25351	(4R)-4-benzyl-1,3-oxazolidin-2-one; (R)-(+)-4-benzyl-2-oxazolidinone	102029-44-7	C₁₀H₁₁NO₂	详情	详情
(III)	63983	(4S)-4-benzyl-3-[(E)-3-(3-fluorophenyl)-2-propenoyl]-1,3-oxazolidin-2-one		C₁₉H₁₆FNO₃	详情	详情
(IV)	25556	N-benzyl-N-(methoxymethyl)-N-[(trimethylsilyl)methyl]amine; N-benzyl-N-(methoxymethyl)(trimethylsilyl)methanamine	1871-96-1	C₁₃H₂₃NOSi	详情	详情
(V)	63985	(4S)-4-benzyl-3-{[(3R,4S)-1-benzyl-4-(3-fluorophenyl)pyrrolidinyl]carbonyl}-1,3-oxazolidin-2-one		C₂₈H₂₇FN₂O₃	详情	详情
(VI)	63984	(4S)-4-benzyl-3-{[(3S,4R)-1-benzyl-4-(3-fluorophenyl)pyrrolidinyl]carbonyl}-1,3-oxazolidin-2-one		C₂₈H₂₇FN₂O₃	详情	详情
(VII)	63986	[(3R,4S)-1-benzyl-4-(3-fluorophenyl)pyrrolidinyl]methanol		C₁₈H₂₀FNO	详情	详情
(VIII)	65130	(3R,4S)-1-benzyl-3-({[tert-butyl(dimethyl)silyl]oxy}methyl)-4-(3-fluorophenyl)pyrrolidine; [(3R,4S)-1-benzyl-4-(3-fluorophenyl)pyrrolidinyl]methyl tert-butyl(dimethyl)silyl ether		C₂₄H₃₄FNOSi	详情	详情
(IX)	63988	(3R,4S)-3-({[tert-butyl(dimethyl)silyl]oxy}methyl)-4-(3-fluorophenyl)pyrrolidine; tert-butyl(dimethyl)silyl [(3R,4S)-4-(3-fluorophenyl)pyrrolidinyl]methyl ether		C₁₇H₂₈FNOSi	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IV)

3-Fluorocinnamic acid (I) is activated as the mixed anhydride (II) with pivaloyl chloride and subsequently coupled to the lithium anion of (S)-4-benzyloxazolidin-2-one (III) to provide the N-acyl oxazolidinone (IV). Cycloaddition of the cinnamoyl derivative (IV) with N-methoxymethyl-N-trimethylsilylmethyl benzylamine (V) in the presence of trifluoroacetic acid gives rise to a diastereomeric mixture of trans-pyrrolidines (VI) and (VII), separable by column chromatography. The desired isomer (VII) is then reduced by LiAlH4 to alcohol (VIII), which is further protected as the silyl ether (IX). Debenzylation of (IX) by transfer hydrogenolysis with ammonium formate and Pearlman's catalyst furnishes pyrrolidine (X).

参考文献中间体

合成目标

【1】 Mills, S.G.; Kim, D.; Hale, J.; MacCoss, M.; Berk, S.; Chapman, K.; Lynch, C.; Caldwell, C.; Willoughby, C.; Kim, R.M. (Merck & Co., Inc.); Pyrrolidine modulators of chemokine receptor activity. US 6498161; WO 0059498 .

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)	63980	m-Fluorocinnamic acid; (E)-3-(3-fluorophenyl)-2-propenoic acid		C₉H₇FO₂	详情	详情
(II)	63981	1,1-dimethylpropanoic (E)-2-(3-fluorophenyl)-2-propenoic anhydride		C₁₄H₁₅FO₃	详情	详情
(III)	63982	(4S)-4-benzyl-1,3-oxazolidin-2-one		C₁₀H₁₁NO₂	详情	详情
(IV)	63983	(4S)-4-benzyl-3-[(E)-3-(3-fluorophenyl)-2-propenoyl]-1,3-oxazolidin-2-one		C₁₉H₁₆FNO₃	详情	详情
(V)	25556	N-benzyl-N-(methoxymethyl)-N-[(trimethylsilyl)methyl]amine; N-benzyl-N-(methoxymethyl)(trimethylsilyl)methanamine	1871-96-1	C₁₃H₂₃NOSi	详情	详情
(VI)	63984	(4S)-4-benzyl-3-{[(3S,4R)-1-benzyl-4-(3-fluorophenyl)pyrrolidinyl]carbonyl}-1,3-oxazolidin-2-one		C₂₈H₂₇FN₂O₃	详情	详情
(VII)	63985	(4S)-4-benzyl-3-{[(3R,4S)-1-benzyl-4-(3-fluorophenyl)pyrrolidinyl]carbonyl}-1,3-oxazolidin-2-one		C₂₈H₂₇FN₂O₃	详情	详情
(VIII)	63986	[(3R,4S)-1-benzyl-4-(3-fluorophenyl)pyrrolidinyl]methanol		C₁₈H₂₀FNO	详情	详情
(IX)	63987	1-[(1S,2S)-4-benzyl-2-propylcyclopentyl]-3-methylbenzene		C₂₂H₂₈	详情	详情
(X)	63988	(3R,4S)-3-({[tert-butyl(dimethyl)silyl]oxy}methyl)-4-(3-fluorophenyl)pyrrolidine; tert-butyl(dimethyl)silyl [(3R,4S)-4-(3-fluorophenyl)pyrrolidinyl]methyl ether		C₁₇H₂₈FNOSi	详情	详情

Extended Information