HRID527485

反应详情

EQUATION

反应方程式

REACTANTS

反应物

HCID392871

1-(tert-Butoxycarbonyl)-4-piperidinecarboxylic acid

C11H19NO4

结构：CCN(C(=O)Oc1ccc(F)cc1)[C@@H]1CN(C(=O)C2CCN(C(=O)OC(C)(C)C)CC2)C[C@H]1c1ccc(Cl)cc1

HCID58312627

未命名化合物

结构：CC(C)N(C(=O)Oc1ccc(F)cc1)[C@@H]1CN(Cc2ccccc2)C[C@H]1c1ccc(Cl)cc1

HCID58312665

未命名化合物

PRODUCTS

生成物

结构：CC(C)N(C(=O)Oc1ccc(F)cc1)[C@@H]1CN(C(=O)C2CCN(C(=O)OC(C)(C)C)CC2)C[C@H]1c1ccc(Cl)cc1

HCID58312654

未命名化合物

PROCEDURE

实验过程

In analogy to the procedure described for the synthesis of rac-4-{(3R,4S)-3-(4-Chloro-phenyl)-4-[ethyl-(4-fluoro-phenoxycarbonyl)-amino]-pyrrolidine-1-carbonyl}-piperidine-1-carboxylic acid tert-butyl ester the title compounds were prepared from rac-[(3S,4R)-1-Benzyl-4-(4-chloro-phenyl)-pyrrolidin-3-yl]-isopropyl-carbamic acid 4-fluoro-phenyl ester by cleavage of the benzyl group and subsequent coupling with 1-(tert-butoxycarbonyl)piperidine-4-carboxylic acid. The resulting rac-4-{(3S,4R)-3-(4-Chloro-phenyl)-4-[(4-fluoro-phenoxycarbonyl)-isopropyl-amino]-pyrrolidine-1-carbonyl}-piperidine-1-carboxylic acid tert-butyl ester was subjected to separation by chiral HPLC on CHIRALPAK AD eluting with i-propanol/heptane. After evaporation of the product containing fractions 4-{(3S,4R)-3-(4-Chloro-phenyl)-4-[(4-fluoro-phenoxycarbonyl)-isopropyl-amino]-pyrrolidine-1-carbonyl}-piperidine-1-carboxylic acid tert-butyl ester was obtained as yellow viscous oil. MS m/e: 588.3 [M+H]+. 4-{(3R,4S)-3-(4-Chloro-phenyl)-4-[(4-fluoro-phenoxycarbonyl)-isopropyl-amino]-pyrrolidine-1-carbonyl}-piperidine-1-carboxylic acid tert-butyl ester was obtained as yellow viscous oil. MS m/e: 588.3 [M+H]+.

WORKUP

后处理

customThe resulting rac-4-{(3S,4R)-3-(4-Chloro-phenyl)-4-[(4-fluoro-phenoxycarbonyl)-isopropyl-amino]-pyrrolidine-1-carbonyl}-piperidine-1-carboxylic acid tert-butyl ester was subjected to separation by chiral HPLC on CHIRALPAK AD
washeluting with i-propanol/heptane
customAfter evaporation of the product
additioncontaining fractions 4-{(3S,4R)-3-(4-Chloro-phenyl)-4-[(4-fluoro-phenoxycarbonyl)-isopropyl-amino]-pyrrolidine-1-carbonyl}-piperidine-1-carboxylic acid tert-butyl ester
customwas obtained as yellow viscous oil

来源与证据

来源类型: Open Reaction Database
ORD 记录: ord-be1745598b0b444eaf216d2eda30e00e
来源数据集: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
专利: US09346786B2
来源说明: uspto-grants-2016_05

反应 SMILES

[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]([N:16]2[CH2:20][C@@H:19]([N:21]([CH2:32][CH3:33])[C:22]([O:24][C:25]3[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=3)=[O:23])[C@H:18]([C:34]3[CH:39]=[CH:38][C:37]([Cl:40])=[CH:36][CH:35]=3)[CH2:17]2)=[O:15])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].F[C:42]1C=CC(OC(=O)N([C@H]2[C@H](C3C=CC(Cl)=CC=3)CN(CC3C=CC=CC=3)C2)C(C)C)=CC=1.C(OC(N1CCC(C(O)=O)CC1)=O)(C)(C)C>>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][CH:11]([C:14]([N:16]2[CH2:20][C@@H:19]([N:21]([C:22]([O:24][C:25]3[CH:26]=[CH:27][C:28]([F:31])=[CH:29][CH:30]=3)=[O:23])[CH:32]([CH3:42])[CH3:33])[C@H:18]([C:34]3[CH:39]=[CH:38][C:37]([Cl:40])=[CH:36][CH:35]=3)[CH2:17]2)=[O:15])[CH2:12][CH2:13]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]