(4R,5S)-4-methyl-5-phenyl-1,3-oxazolidin-2-one -Drug Synthesis Database

【结构式】

【分子编号】26040

【品名】(4R,5S)-4-methyl-5-phenyl-1,3-oxazolidin-2-one

【CA登记号】

【分子式】C₁₀H₁₁NO₂

【分子量】177.20288

【元素组成】C 67.78% H 6.26% N 7.9% O 18.06%

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)

1) The reaction of 4-methylpentanoic acid (I) with SOCl2 in refluxing chloroform gives the acyl chloride (II), which is condensed with the chiral oxazolidinone (III) by means of BuLi in THF, yielding the corresponding N-acyl derivative (IV). The regioselective alkylation of (IV) with benzyl bromoacetate (V) by means of LDA in THF affords the (S)-adduct (VI) with >95% e.e. purity. The elimination of the chiral auxiliary with LiOH and H2O2 gives the glutaric acid monoester (VII), which is reduced with BH3/SMe2 in THF, yielding compound (VIII). The reaction of (VIII) with tosyl chloride in pyridine yields the tosylate (IX), which is treated with sodium azide in DMSO, affording the azide (X). Finally, this compound is reduced and debenzylated with H2 over Pd/C in THF.

参考文献中间体

合成目标

【1】 Bryans, J.S.; Wustrow, D.J.; 3-Substituted GABA analogs with central nervous system activity: A review. Med Res Rev 1999, 19, 2, 149.
【2】 Newhouse, B.J.; Ibrahim, P.; Burgess, L.E.; et al.; Potent selective nonpeptidic inhibitors of human lung tryptase. Proc Natl Acad Sci USA 1999, 96, 15, 8348.
【3】 Sobieray, D.M.; Hoekstra, M.S.; Schwindt, M.A.; et al.; Chemical development of CI-1008, an enantiomerically pure anticonvulsant. Org Process Res Dev 1997, 1, 1, 26.
【4】 Taylor, C.P.; Kanter, G.D.; Vartanian, M.G.; Yuen, P.; Enantioselective synthesis of PD144723: A potent stereospecific anticonvulsant. Bioorg Med Chem Lett 1994, 4, 6, 823.

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)	25389	4-methylpentanoic acid	646-07-1	C₆H₁₂O₂	详情	详情
(II)	25390	4-methylpentanoyl chloride	38136-29-7	C₆H₁₁ClO	详情	详情
(III)	26040	(4R,5S)-4-methyl-5-phenyl-1,3-oxazolidin-2-one		C₁₀H₁₁NO₂	详情	详情
(IV)	26041	(4R,5S)-4-methyl-3-(4-methylpentanoyl)-5-phenyl-1,3-oxazolidin-2-one		C₁₆H₂₁NO₃	详情	详情
(V)	12869	benzyl 2-bromoacetate	5437-45-6	C₉H₉BrO₂	详情	详情
(VI)	26042	benzyl (3S)-5-methyl-3-[[(4R,5S)-4-methyl-2-oxo-5-phenyl-1,3-oxazolidin-3-yl]carbonyl]hexanoate		C₂₅H₂₉NO₅	详情	详情
(VII)	26043	(2S)-2-[2-(benzyloxy)-2-oxoethyl]-4-methylpentanoic acid		C₁₅H₂₀O₄	详情	详情
(VIII)	26044	benzyl (3S)-3-(hydroxymethyl)-5-methylhexanoate		C₁₅H₂₂O₃	详情	详情
(IX)	26045	benzyl (3S)-5-methyl-3-([[(4-methylphenyl)sulfonyl]oxy]methyl)hexanoate		C₂₂H₂₈O₅S	详情	详情
(X)	26046	benzyl (3S)-3-(azidomethyl)-5-methylhexanoate		C₁₅H₂₁N₃O₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(III)

2) The reaction of 4-methylpentanoic acid (I) with SOCl2 in refluxing chloroform gives the acyl chloride (II), which is condensed with the chiral oxazolidinone (III) by means of BuLi in THF, yielding the corresponding N-acyl derivative (IV). The regioselective alkylation of (IV) with tert-butyl bromoacetate (XI) by means of LDA in THF affords the (S)-adduct (XII). The elimination of the chiral auxiliary with LiOH and H2O2 gives the glutaric acid monoester (XIII), which is reduced with BH3/SMe2 in THF, yielding compound (XIV). The reaction of (XIV) with tosyl chloride in pyridine yields the tosylate (XV), which is treated with sodium azide in DMSO, affording the azide (XVI). The hydrolysis of the tert-butyl group of (XVI) affords the free acid (XVII), which is reduced with H2 over Pd/C.

参考文献中间体

合成目标

【1】 Newhouse, B.J.; Ibrahim, P.; Burgess, L.E.; et al.; Potent selective nonpeptidic inhibitors of human lung tryptase. Proc Natl Acad Sci USA 1999, 96, 15, 8348.
【2】 Sobieray, D.M.; Hoekstra, M.S.; Schwindt, M.A.; et al.; Chemical development of CI-1008, an enantiomerically pure anticonvulsant. Org Process Res Dev 1997, 1, 1, 26.

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)	25389	4-methylpentanoic acid	646-07-1	C₆H₁₂O₂	详情	详情
(II)	25390	4-methylpentanoyl chloride	38136-29-7	C₆H₁₁ClO	详情	详情
(III)	26040	(4R,5S)-4-methyl-5-phenyl-1,3-oxazolidin-2-one		C₁₀H₁₁NO₂	详情	详情
(IV)	26041	(4R,5S)-4-methyl-3-(4-methylpentanoyl)-5-phenyl-1,3-oxazolidin-2-one		C₁₆H₂₁NO₃	详情	详情
(XI)	17430	2-Bromoacetic acid tert-butyl ester; tert-butyl 2-bromoacetate; tert-Butyl bromoacetate	5292-43-3	C₆H₁₁BrO₂	详情	详情
(XII)	26047	tert-butyl (3S)-5-methyl-3-[[(4R,5S)-4-methyl-2-oxo-5-phenyl-1,3-oxazolidin-3-yl]carbonyl]hexanoate		C₂₂H₃₁NO₅	详情	详情
(XIII)	25393	(2R)-2-[2-(tert-butoxy)-2-oxoethyl]-4-methylpentanoic acid		C₁₂H₂₂O₄	详情	详情
(XIV)	26048	tert-butyl (3S)-3-(hydroxymethyl)-5-methylhexanoate		C₁₂H₂₄O₃	详情	详情
(XV)	26049	tert-butyl (3S)-5-methyl-3-([[(4-methylphenyl)sulfonyl]oxy]methyl)hexanoate		C₁₉H₃₀O₅S	详情	详情
(XVI)	26050	tert-butyl (3S)-3-(azidomethyl)-5-methylhexanoate		C₁₂H₂₃N₃O₂	详情	详情
(XVII)	26051	(3S)-3-(azidomethyl)-5-methylhexanoic acid		C₈H₁₅N₃O₂	详情	详情

Extended Information