Sodium hydride → (3S,4S)-3-[(5-chloro-thiophene-2-carbonyl)-amino]-4-(2,2-difluoro-ethoxy)-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 1162640노트

반응식

HRID 1162640 반응식
[H-].[Na+].[C:3]([O:7][C:8]([N:10]1[CH2:14][C@H:13]([OH:15])[C@@H:12]([NH:16][C:17]([C:19]2[S:20][C:21]([Cl:24])=[CH:22][CH:23]=2)=[O:18])[CH2:11]1)=[O:9])([CH3:6])([CH3:5])[CH3:4].FC(F)(F)S(O[CH2:31][CH:32]([F:34])[F:33])(=O)=O>CN(C=O)C.CCOC(C)=O>[C:3]([O:7][C:8]([N:10]1[CH2:14][C@H:13]([O:15][CH2:31][CH:32]([F:34])[F:33])[C@@H:12]([NH:16][C:17]([C:19]2[S:20][C:21]([Cl:24])=[CH:22][CH:23]=2)=[O:18])[CH2:11]1)=[O:9])([CH3:6])([CH3:4])[CH3:5]

참가 물질

6

반응물 3

HCID 24758Sodium hydrideHCID 27740892,2-Difluoroethyl trifluoromethanesulfonateHCID 42643219(3S,4S)-3-[(5-chloro-thiophene-2-carbonyl)-amino]-4-hydroxy-pyrrolidine-1-carboxylic acid tert-butyl ester

생성물 1

HCID 42643221(3S,4S)-3-[(5-chloro-thiophene-2-carbonyl)-amino]-4-(2,2-difluoro-ethoxy)-pyrrolidine-1-carboxylic acid tert-butyl ester수율 49.1%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

실험 절차

30.1 A suspension of 37 mg NaH (55% in oil) in 2 ml DMF was treated at 0° C. under an argon atmosphere with a solution of 270 mg (3S,4S)-3-[(5-chloro-thiophene-2-carbonyl)-amino]-4-hydroxy-pyrrolidine-1-carboxylic acid tert-butyl ester (example 22.4). The reaction mixture was stirred for 1 hr at r.t. Then, 334 mg 2,2-difluoroethyl trifluoromethanesulfonate were added at 0° C. The reaction mixture was stirred for 2 days at r.t., then diluted with EtOAc and washed with water. The organic layer was dried over MgSO4, filtered and concentrated. The crude product was isolated by chromatography (silica gel; gradient: cyclohexane->cyclohexane/EtOAc 9:1) to give 157 mg (3S,4S)-3-[(5-chloro-thiophene-2-carbonyl)-amino]-4-(2,2-difluoro-ethoxy)-pyrrolidine-1-carboxylic acid tert-butyl ester. Colorless solid. MS 409.0 ([M+H]+)

후처리

  1. stirringThe reaction mixture was stirred for 2 days at r.t.
  2. washwashed with water
  3. dry with materialThe organic layer was dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude product was isolated by chromatography (silica gel; gradient: cyclohexane->cyclohexane/EtOAc 9:1)

출처 및 근거

ORD 기록
ord-f58407d375f543efb37c7c551a8a86a3
출처 데이터셋
uspto-grants-2010_10
특허 번호
US07820699B2

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