【结 构 式】 |
【分子编号】38797 【品名】benzyl (1R)-2-(benzylamino)-1-(hydroxymethyl)-2-oxoethylcarbamate 【CA登记号】 |
【 分 子 式 】C18H20N2O4 【 分 子 量 】328.36788 【元素组成】C 65.84% H 6.14% N 8.53% O 19.49% |
合成路线1
该中间体在本合成路线中的序号:(VI)D-Serine (I) was protected as the N-benzyloxycarbonyl derivative (II) by means of benzyl chloroformate in the presence of MgO. Methylation of the alcohol hydroxyl of (II) under Williamson conditions using iodomethane and Ag2O also produced esterification of the carboxyl group to give (III), which was further hydrolyzed to carboxylic acid (IV) with K2CO3 in MeOH-H2O. After activation of (IV) as the mixed anhydride with isobutyl chloroformate, coupling with benzyl amine furnished amide (V). This was alternatively obtained through a related procedure involving coupling of N-Cbz-serine (II) with benzylamine, followed by O-methylation of the resulting hydroxy amide (VI) with iodomethane and Ag2O. Finally, the N-carbobenzoxy protecting group of (V) was removed by catalytic hydrogenolysis in the presence of Pd/C.
【1】 Andurkar, S.V.; et al.; Synthesis and anticonvulsant activities of (R)-(O)-methylserine derivatives. Tetrahedron Asymmetry 1998, 9, 21, 3841. |
【2】 Kohn, H.; Andurkar, S.V. (Research Corporation Technologies, Inc.); Anticonvulsant enantiomeric amino acid derivs.. US 6048899; WO 0000463 . |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
10101 | Benzyloxycarbonyl chloride; Benzyl chloroformate; 1-[[(Chlorocarbonyl)oxy]methyl]benzene | 501-53-1 | C8H7ClO2 | 详情 | 详情 | |
15147 | Benzylamine; Phenylmethanamine | 100-46-9 | C7H9N | 详情 | 详情 | |
(I) | 15728 | (+)-2-Amino-3-hydroxypropionic acid; D-(+)-Serine; D-serine | 312-84-5 | C3H7NO3 | 详情 | 详情 |
(II) | 32794 | (2S)-2-[[(benzyloxy)carbonyl]amino]-3-hydroxypropionic acid | C11H13NO5 | 详情 | 详情 | |
(III) | 38794 | methyl (2R)-2-[[(benzyloxy)carbonyl]amino]-3-methoxypropanoate | C13H17NO5 | 详情 | 详情 | |
(IV) | 38795 | (2R)-2-[[(benzyloxy)carbonyl]amino]-3-methoxypropionic acid | C12H15NO5 | 详情 | 详情 | |
(V) | 38796 | benzyl (1R)-2-(benzylamino)-1-(methoxymethyl)-2-oxoethylcarbamate | C19H22N2O4 | 详情 | 详情 | |
(VI) | 38797 | benzyl (1R)-2-(benzylamino)-1-(hydroxymethyl)-2-oxoethylcarbamate | C18H20N2O4 | 详情 | 详情 |