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【结 构 式】

【分子编号】27401

【品名】ethyl (2R,4R)-4-hydroxy-2-pyrrolidinecarboxylate

【CA登记号】

【 分 子 式 】C7H13NO3

【 分 子 量 】159.18516

【元素组成】C 52.82% H 8.23% N 8.8% O 30.15%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(II)

The esterification of (2R,4R)-4-hydroxypyrrolidine-2-carboxylic acid (I) with ethanol and sulfuric acid gives the expected ethyl ester (II), which is N-protected with benzyl bromide and DIEA in dichloromethane to the N-benzyl derivative (III). The oxidation of (III) with oxalyl chloride in DMSO affords the pyrrolidinone (IV), which is cyclized with ammonium carbamate and KCN in hot ethanol/water to afford the spiro imidazolidinedione (V). Opening of the imidazolidinedione ring of (V) with refluxing 3N NaOH, followed by esterification with ethanol/SOCl2 provides (2R,4R)-4-amino-1-benzylpyrrolidine-2,4-dicarboxylic acid diethyl ester (VI), which is protected at the amino group with tert-butoxycarbonyl anhydride giving the carbamate (VII) (1). Hydrogenolysis of the N-benzyl group of (VII) in the presence of Pd/C yields (VIII) with a free imino group, which is alkylated with 1-(chloromethyl)naphthalene (IX) by means of DIEA and Bu4NI affording the naphthylmethyl derivative (X). Removal of the Boc protecting group of (X) with HCl in ethyl ether gives (2R,4R)-4-amino-1-(1-naphthylmethyl)pyrrolidine-2,4-dicarboxylic acid diethyl ester (XI), which is finally hydrolyzed with NaOH to the target diacid (2).

1 Valli, M.J.; Schoepp, D.D.; Wright, R.A.; Johnson, B.G.; Kingston, A.E.; Tomlinson, R.; Monn, J.A.; Synthesis and metabotropic glutamate receptor antagonist activity of N'-substituted analogs of 2R,4R-4-aminopyrrolidine-2,4-dicarboxylic acid. Bioorg Med Chem Lett 1998, 8, 15, 1985.
2 Monn, J.A.; et al.; Synthesis of the four isomers of 4-aminopyrrolidine-2,4-dicarboxylate: Identification of a potent, highly selective, and systemically-active agonist for metabotropic glutamate receptors negatively coupled to adenylate cyclase. J Med Chem 1996, 39, 15, 2990.
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) 27400 (2R,4R)-4-hydroxy-2-pyrrolidinecarboxylic acid C5H9NO3 详情 详情
(II) 27401 ethyl (2R,4R)-4-hydroxy-2-pyrrolidinecarboxylate C7H13NO3 详情 详情
(III) 27402 ethyl (2R,4R)-1-benzyl-4-hydroxy-2-pyrrolidinecarboxylate C14H19NO3 详情 详情
(IV) 27403 ethyl (2R)-1-benzyl-4-oxo-2-pyrrolidinecarboxylate C14H17NO3 详情 详情
(V) 27404 ethyl (8R)-7-benzyl-2,4-dioxo-1,3,7-triazaspiro[4.4]nonane-8-carboxylate C16H19N3O4 详情 详情
(VI) 27405 diethyl (2R,4R)-4-amino-1-benzyl-2,4-pyrrolidinedicarboxylate C17H24N2O4 详情 详情
(VII) 27406 diethyl (2R,4R)-1-benzyl-4-[(tert-butoxycarbonyl)amino]-2,4-pyrrolidinedicarboxylate C22H32N2O6 详情 详情
(VIII) 27407 diethyl (2R,4R)-4-[(tert-butoxycarbonyl)amino]-2,4-pyrrolidinedicarboxylate C15H26N2O6 详情 详情
(IX) 27408 1-(Chloromethyl)naphthalene 86-52-2 C11H9Cl 详情 详情
(X) 27409 diethyl (2R,4R)-4-[(tert-butoxycarbonyl)amino]-1-(1-naphthylmethyl)-2,4-pyrrolidinedicarboxylate C26H34N2O6 详情 详情
(XI) 27410 diethyl (2R,4R)-4-amino-1-(1-naphthylmethyl)-2,4-pyrrolidinedicarboxylate C21H26N2O4 详情 详情
Extended Information