• English
  • 简体中文
Login Register
Current Location: Home > Feedback Help Print

【结 构 式】

【分子编号】50569

【品名】(4S)-4-isopropyl-5-oxotetrahydro-2-furancarbonyl chloride

【CA登记号】

【 分 子 式 】C8H11ClO3

【 分 子 量 】190.62624

【元素组成】C 50.41% H 5.82% Cl 18.6% O 25.18%

与该中间体有关的原料药合成路线共 2 条

合成路线1

该中间体在本合成路线中的序号:(XXV)

The intermediate gamma-butyrolactone (XXVIII) has been obtained as follows: Allylation of the imidazolidinone intermediate (V) with allyl bromide (XXI) and LiHMDS in THF gives the chiral intermediate (XXII), which by dihydroxylation and cleavage of the chiral auxiliary with OsO4 and NMMO in tert-butanol/acetone/water yields the lactone alcohol (XXIII). Oxidation of (XXIII) with NaIO4 and RuCl3 in CCl4/acetonitrile/water affords the carboxylic acid (XXIV), which by treatment with (COCl)2 in toluene provides the acyl chloride (XXV). Esterification of (XXV) with benzyl alcohol gives the corresponding benzyl ester as a diastereomeric mixture, from which the desired isomer (XXVI) is separated by flash chromatography. Hydrogenolysis of the benzyl ester (XXVI) with H2 over Pd/C in ethyl acetate yields the carboxylic acid (XXVII), which is treated with oxalyl chloride in toluene to afford the desired gamma-butyrolactone intermediate (XXVIII).

1 Mealy, N.E.; Castañer, R.M.; Silvestre, J.S.; Castañer, J.; Aliskiren Fumarate. Drugs Fut 2001, 26, 12, 1139.
2 Rüeger, H.; Maibaum, J.; Stutz, S.; Spindler, F.; Göschke, R.; A convergent synthesis approach towards CGP60536B, a non-peptide orally potent renin inhibitor, via an enantiomerically pure ketolactone intermediate. Tetrahedron Lett 2000, 41, 51, 10085.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(V) 28131 (4S)-4-benzyl-3-(3-methylbutanoyl)-1,3-oxazolidin-2-one C15H19NO3 详情 详情
(XXI) 11463 3-Bromo-1-propene; 3-Bromopropene;allyl bromide 106-95-6 C3H5Br 详情 详情
(XXII) 50566 (4S)-4-benzyl-3-[(2S)-2-isopropyl-4-pentenoyl]-1,3-oxazolidin-2-one C18H23NO3 详情 详情
(XXIII) 50567 (3S)-5-(hydroxymethyl)-3-isopropyldihydro-2(3H)-furanone C8H14O3 详情 详情
(XXIV) 50568 (4S)-4-isopropyl-5-oxotetrahydro-2-furancarboxylic acid C8H12O4 详情 详情
(XXV) 50569 (4S)-4-isopropyl-5-oxotetrahydro-2-furancarbonyl chloride C8H11ClO3 详情 详情
(XXVI) 50570 benzyl (2S,4S)-4-isopropyl-5-oxotetrahydro-2-furancarboxylate C15H18O4 详情 详情
(XXVII) 50571 (2S,4S)-4-isopropyl-5-oxotetrahydro-2-furancarboxylic acid C8H12O4 详情 详情
(XXVIII) 50572 (2S,4S)-4-isopropyl-5-oxotetrahydro-2-furancarbonyl chloride C8H11ClO3 详情 详情

合成路线2

该中间体在本合成路线中的序号:(IV)

 

1 Rueger H, Stutz S, Goschke R, et al. 2000. A convergent synthesisi approach towards CGP60536B, a nonpeptide orally potent renin inhibitory, via an enantiomerically pure keto lactone intermediate. Tetrahedron Lett, 41(51): 10085~10089
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) 28131 (4S)-4-benzyl-3-(3-methylbutanoyl)-1,3-oxazolidin-2-one C15H19NO3 详情 详情
(II) 50566 (4S)-4-benzyl-3-[(2S)-2-isopropyl-4-pentenoyl]-1,3-oxazolidin-2-one C18H23NO3 详情 详情
(III) 50567 (3S)-5-(hydroxymethyl)-3-isopropyldihydro-2(3H)-furanone C8H14O3 详情 详情
(IV) 50569 (4S)-4-isopropyl-5-oxotetrahydro-2-furancarbonyl chloride C8H11ClO3 详情 详情
(V) 67008 benzyl (2S,4R)-4-isopropyl-5-oxotetrahydro-2-furancarboxylate   C15H18O4 详情 详情
(VI) 50570 benzyl (2S,4S)-4-isopropyl-5-oxotetrahydro-2-furancarboxylate C15H18O4 详情 详情
(VII) 50571 (2S,4S)-4-isopropyl-5-oxotetrahydro-2-furancarboxylic acid C8H12O4 详情 详情
(VIII) 50572 (2S,4S)-4-isopropyl-5-oxotetrahydro-2-furancarbonyl chloride C8H11ClO3 详情 详情
(IX) 28119 (2R)-2-[4-methoxy-3-(3-methoxypropoxy)benzyl]-3-methylbutyric acid C17H26O5 详情 详情
(X) 50573 (2R)-2-[4-methoxy-3-(3-methoxypropoxy)benzyl]-3-methyl-1-butanol C17H28O4 详情 详情
(XI) 50574 4-[(2R)-2-(chloromethyl)-3-methylbutyl]-1-methoxy-2-(3-methoxypropoxy)benzene; 3-[5-[(2R)-2-(chloromethyl)-3-methylbutyl]-2-methoxyphenoxy]propyl methyl ether 324763-39-5 C17H27ClO3 详情 详情
(XII) 50575 (3S,5S)-3-isopropyl-5-[(3S)-3-[4-methoxy-3-(3-methoxypropoxy)benzyl]-4-methylpentanoyl]dihydro-2(3H)-furanone C25H38O6 详情 详情
(XIII) 50576 (3S,5S)-5-[(1R,3S)-1-hydroxy-3-[4-methoxy-3-(3-methoxypropoxy)benzyl]-4-methylpentyl]-3-isopropyldihydro-2(3H)-furanone C25H40O6 详情 详情
(XIV) 50578 (3S,5S)-5-[(1S,3S)-1-azido-3-[4-methoxy-3-(3-methoxypropoxy)benzyl]-4-methylpentyl]-3-isopropyldihydro-2(3H)-furanone C25H39N3O5 详情 详情
(XV) 28129 3-amino-2,2-dimethylpropanamide 324763-51-1 C5H12N2O 详情 详情
(XVI) 50579 (2S,4S,5S,7S)-N-(4-amino-2,2-dimethyl-4-oxobutyl)-5-azido-4-hydroxy-2-isopropyl-7-[4-methoxy-3-(3-methoxypropoxy)benzyl]-8-methylnonanamide C31H53N5O6 详情 详情
Extended Information