Methyl chloroformate → HCID 42633348, 화합물

HRID 409427노트

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HRID 409427 반응식
[C:1]([O:5][C:6]([N:8]1[C@H:12]([CH2:13][CH3:14])[CH2:11][C@H:10]([NH:15][CH2:16][C:17]2[CH:22]=[C:21]([C:23]([F:26])([F:25])[F:24])[CH:20]=[C:19]([C:27]([F:30])([F:29])[F:28])[CH:18]=2)[C@@H:9]1[CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])[O-].[Cs+].[Cs+].Cl[C:45]([O:47][CH3:48])=[O:46].CCOC(C)=O>C(#N)C.[Cl-].[Na+].O>[C:1]([O:5][C:6]([N:8]1[C@H:12]([CH2:13][CH3:14])[CH2:11][C@H:10]([N:15]([CH2:16][C:17]2[CH:22]=[C:21]([C:23]([F:25])([F:24])[F:26])[CH:20]=[C:19]([C:27]([F:30])([F:28])[F:29])[CH:18]=2)[C:45]([O:47][CH3:48])=[O:46])[C@@H:9]1[CH2:31][C:32]1[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

참가 물질

7

반응물 4

HCID 6586Methyl chloroformate2회HCID 8857Ethyl AcetateHCID 10796Cesium carbonateHCID 59614365HCID 59614365, 화합물

생성물 1

HCID 42633348HCID 42633348, 화합물수율 52%

시약·촉매·용매 2

HCID 6342Acetonitrile용매HCID 57417360Sodium chloride; water용매

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온도
80 °C

실험 절차

To a solution of (2S,3S,5R)-2-benzyl-3-(3,5-bis-trifluoromethyl-benzylamino)-5-ethyl-pyrrolidine-1-carboxylic acid tert-butyl ester (0.0377 mmol; 20 mg) and cesium carbonate (0.113 mmol; 36.8 mg) in acetonitrile (0.38 mL) is added methyl chloroformate (0.0754 mmol; 5.9 mg) at room temperature. The reaction mixture is warmed to 80° C. and stirred for 3.5 hours. Additional methyl chloroformate (0.0754 mmol; 5.9 mg) is added to the mixture, and the mixture is stirred for additional 0.5 hours, and then cooled to room temperature. To the mixture is added brine and EtOAc. The organic layer is separated, dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue is purified by preparative thin layer chromatography on silica gel (eluent: n-hexane/EtOAc) to give (2S,3S,5R)-2-Benzyl-3-[(3,5-bis-trifluoromethyl-benzyl)-methoxycarbonyl-amino]-5-ethyl-pyrrolidine-1-carboxylic acid tert-butyl ester (11.5 mg, 52%); ESI-MS m/z: 589 [M+1]+, Retention time 2.63 min (condition A).

후처리

  1. stirringthe mixture is stirred for additional 0.5 hours
  2. temperaturecooled to room temperature
  3. customThe organic layer is separated
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue is purified by preparative thin layer chromatography on silica gel (eluent: n-hexane/EtOAc)

출처 및 근거

ORD 기록
ord-5e7054397440409c987ff509d9abb056
출처 데이터셋
uspto-grants-2014_06
특허 번호
US08759365B2

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