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

HRID 1527320ノート

反応式

HRID 1527320 の反応式
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]

参加物

6

反応物 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

生成物 1

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

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-6bd16d27bf8e41218f03e5059dcfc77b
出典データセット
uspto-grants-2015_07
特許番号
US09085555B2

反応ノート

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