2-butylmalonic acid -Drug Synthesis Database

【结构式】

【分子编号】45891

【品名】2-butylmalonic acid

【CA登记号】534-59-8

【分子式】C₇H₁₂O₄

【分子量】160.16988

【元素组成】C 52.49% H 7.55% O 39.96%

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：(XI)

Alternatively, compound (R)-(IX) can be obtained as follows: treatment of butylmalonic acid (XI) with formaldehyde (XII) in ethanol in the presence of piperidine provides 2-butyl acrylic acid (XIII), which is converted into oxazolidinone derivative (XVI) by first reaction with pivaloyl chloride (XIV) and Et3N in THF followed by treatment with derivative (XV) and BuLi in THF. Oxazolidinone (XVI) is then enantioselectively condensed with O-benzylhydroxylamine (XVII) and treated with p-TsOH to afford a single diastereoisomer (XVIII), which is then hydrolyzed with LiOH in THF to yield (XIX). Finally, hexanoic acid (XIX) is coupled to tert-Leucine-N,N-dimethylamide (VII) by means of EDC and HOBt in DMF.

参考文献中间体

合成目标

【1】 Spavold, Z.M.; Launchbury, S.; Clements, J.M.; Hunter, M.G.; Davies, S.J.; Pratt, L.M.; Beckett, R.P.; Whittaker, M. (British Biotech Pharmaceuticals Ltd.); Antibacterial agents. WO 9939704 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VII)	45886	(2S)-2-amino-N,N,3,3-tetramethylbutanamide		C₈H₁₈N₂O	详情	详情
(IX)	45888	(2R)-2-[[(benzyloxy)amino]methyl]-N-[(1S)-1-[(dimethylamino)carbonyl]-2,2-dimethylpropyl]hexanamide		C₂₂H₃₇N₃O₃	详情	详情
(XI)	45891	2-butylmalonic acid	534-59-8	C₇H₁₂O₄	详情	详情
(XII)	22075	Formaldehyde; Paraformaldehyde	1118-66-7	CH₂O	详情	详情
(XIII)	45892	2-[(ethylsulfanyl)methyl]acrylic acid		C₆H₁₀O₂S	详情	详情
(XIV)	13597	2,2-Dimethylpropanoyl chloride; Pivaloyl chloride	3282-30-2	C₅H₉ClO	详情	详情
(XV)	45893	(4S)-4-benzyl-5,5-dimethyl-1,3-oxazolidin-2-one		C₁₂H₁₅NO₂	详情	详情
(XVI)	45894	(4S)-4-benzyl-3-[2-[(ethylsulfanyl)methyl]acryloyl]-5,5-dimethyl-1,3-oxazolidin-2-one		C₁₈H₂₃NO₃S	详情	详情
(XVII)	14640	O-benzylhydroxylamine; 1-[(aminooxy)methyl]benzene	622-33-3	C₇H₉NO	详情	详情
(XVIII)	45895	(4S)-4-benzyl-3-[(2R)-3-[(benzyloxy)amino]-2-[(ethylsulfanyl)methyl]propanoyl]-5,5-dimethyl-1,3-oxazolidin-2-one		C₂₅H₃₂N₂O₄S	详情	详情
(XIX)	45897	3-[4-[2-(benzyloxy)ethoxy]phenyl]-2-ethoxypropanamide		C₂₀H₂₅NO₄	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

The reaction of 2-butylmalonic acid (I) with piperidine and formaldehyde in refluxing ethanol gives 2-methylenehexanoic acid (II), which is condensed with the chiral auxiliary oxazolidine lithium salt (III) by means of pivaloyl chloride and TEA to yield the oxazolidide (IV). The addition of O-benzylhydroxylamine (V) to (IV) by means of Ts-OH proceeds with great stereospecificity, affording tosylate (VI), which is submitted to cleavage of the chiral auxiliary with LiOH in aqueous THF to provide the carboxylic acid (VII). The formylation of the benzylhydroxylamine group of (VII) with HCOO-Ac in THF gives the formamide (VIII), which is condensed with L-tert-leucine dimethylamide (IX) by means of HOAt and EDC in DMF to yield the pseudo dipeptide (X). Finally, this compound is debenzylated by hydrogenation with H2 over Pd/C in ethanol.

参考文献中间体

合成目标

【1】 Pratt, L.M.; et al.; Asymmetric synthesis of BB-3497 - A potent peptide deformylase inhibitor. Bioorg Med Chem Lett 2001, 11, 19, 2585.

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)	45891	2-butylmalonic acid	534-59-8	C₇H₁₂O₄	详情	详情
(II)	51559	2-butylacrylic acid		C₇H₁₂O₂	详情	详情
(III)	51560	[(4S)-4-benzyl-5,5-dimethyl-2-oxo-1,3-oxazolidin-3-yl]lithium		C₁₂H₁₄LiNO₂	详情	详情
(IV)	51561	(4S)-4-benzyl-3-(2-butylacryloyl)-5,5-dimethyl-1,3-oxazolidin-2-one		C₁₉H₂₅NO₃	详情	详情
(V)	14640	O-benzylhydroxylamine; 1-[(aminooxy)methyl]benzene	622-33-3	C₇H₉NO	详情	详情
(VI)	51562	(2R)-2-[[(4S)-4-benzyl-5,5-dimethyl-2-oxo-1,3-oxazolidin-3-yl]carbonyl]-N-(benzyloxy)-1-hexanaminium 4-methylbenzenesulfonate		C₃₃H₄₂N₂O₇S	详情	详情
(VII)	51563	(2R)-2-[[(benzyloxy)amino]methyl]hexanoic acid		C₁₄H₂₁NO₃	详情	详情
(VIII)	51564	(2R)-2-[[(benzyloxy)(formyl)amino]methyl]hexanoic acid		C₁₅H₂₁NO₄	详情	详情
(IX)	45886	(2S)-2-amino-N,N,3,3-tetramethylbutanamide		C₈H₁₈N₂O	详情	详情
(X)	45889	(2R)-2-[[(benzyloxy)(formyl)amino]methyl]-N-[(1S)-1-[(dimethylamino)carbonyl]-2,2-dimethylpropyl]hexanamide		C₂₃H₃₇N₃O₄	详情	详情

Extended Information