Methyl chloroformate → HCID 42633348、化合物

HRID 409427ノート

反応式

HRID 409427 の反応式
[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]

参加物

7

反応物 4

HCID 6586Methyl chloroformate2 回HCID 8857Ethyl AcetateHCID 10796Cesium carbonateHCID 59614365HCID 59614365、化合物

生成物 1

HCID 42633348HCID 42633348、化合物収率 52%

試薬・触媒・溶媒 2

HCID 6342Acetonitrile溶媒HCID 57417360Sodium chloride; water溶媒

反応条件

温度
80 °C

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-5e7054397440409c987ff509d9abb056
出典データセット
uspto-grants-2014_06
特許番号
US08759365B2

反応ノート

読み込み中…