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【结 构 式】 
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【分子编号】50566 【品名】(4S)-4-benzyl-3-[(2S)-2-isopropyl-4-pentenoyl]-1,3-oxazolidin-2-one 【CA登记号】 |
【 分 子 式 】C18H23NO3 【 分 子 量 】301.38556 【元素组成】C 71.73% H 7.69% N 4.65% O 15.93% |
合成路线1
该中间体在本合成路线中的序号：(XXII)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：(II)
| 【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 |