Methanol → (3S,5S)-5-(3-Chloro-2-fluoro-benzylcarbamoyl)-pyrrolidine-1,3-dicarboxylic acid 1-tert-butyl ester 3-methyl ester

HRID 1527320노트

반응식

HRID 1527320 반응식
Cl[Si](C)(C)C.C[OH:7].[C:8]([O:12][C:13]([N:15]1[CH2:19][C@@H:18]([C:20]#N)[CH2:17][C@H:16]1[C:22](=[O:33])[NH:23][CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[C:27]([Cl:31])[C:26]=1[F:32])=[O:14])([CH3:11])([CH3:10])[CH3:9].[C:34](OC(OC(C)(C)C)=O)(OC(C)(C)C)=[O:35]>C(Cl)Cl>[CH3:34][O:35][C:20]([C@H:18]1[CH2:17][C@@H:16]([C:22](=[O:33])[NH:23][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[C:27]([Cl:31])[C:26]=2[F:32])[N:15]([C:13]([O:12][C:8]([CH3:9])([CH3:11])[CH3:10])=[O:14])[CH2:19]1)=[O:7]

참가 물질

6

반응물 4

HCID 887MethanolHCID 6397ChlorotrimethylsilaneHCID 90495Di-tert-butyl dicarbonateHCID 68283946(2S,4S)-2-(3-Chloro-2-fluoro-benzylcarbamoyl)-4-cyano-pyrrolidine-1-carboxylic acid tert-butyl ester

생성물 1

HCID 68284043(3S,5S)-5-(3-Chloro-2-fluoro-benzylcarbamoyl)-pyrrolidine-1,3-dicarboxylic acid 1-tert-butyl ester 3-methyl ester

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

Chlorotrimethylsilane (5.66 mL, 44.8 mmol) was added dropwise to dry MeOH (7.6 mL) at 0° C. followed by a solution of (2S,4S)-2-(3-chloro-2-fluoro-benzylcarbamoyl)-4-cyano-pyrrolidine-1-carboxylic acid tert-butyl ester (900 mg, 2.36 mmol) in dry CH2Cl2 (6.7 mL) and the resulting mixture was stirred at RT for 5 h. The mixture was cooled to 0° C., quenched with a saturated aqueous solution of NaHCO3 and extracted with CH2Cl2 (×3). To the organic extracts was added di-tert-butyl dicarbonate (514 mg, 2.36 mmol) at RT and the resulting solution was stirred overnight. The reaction mixture was concentrated in vacuo and the crude material purified by flash column chromatography (c-hexane to c-hexane/EtOAc 1:1) to give the expected compound. tR (HPLC conditions a): 3.50 min.

후처리

  1. temperatureThe mixture was cooled to 0° C.
  2. customquenched with a saturated aqueous solution of NaHCO3
  3. extractionextracted with CH2Cl2 (×3)
  4. stirringthe resulting solution was stirred overnight
  5. concentrationThe reaction mixture was concentrated in vacuo
  6. customthe crude material purified by flash column chromatography (c-hexane to c-hexane/EtOAc 1:1)

출처 및 근거

ORD 기록
ord-6bd16d27bf8e41218f03e5059dcfc77b
출처 데이터셋
uspto-grants-2015_07
특허 번호
US09085555B2

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