Cesium carbonate → (2R,5R)-5-{(1S,2S)-2-Acetylamino-3-[3-(2,2-difluoroethoxy)-phenyl]-1-hydroxypropyl}-2-(1-methylcyclopentylmethoxy)-morpholine-4-carboxylic acid tert-butyl ester

HRID 20429

反応式

HRID 20429 の反応式
[C:1]([O:5][C:6]([N:8]1[C@@H:13]([C@@H:14]([OH:28])[C@@H:15]([NH:24][C:25](=[O:27])[CH3:26])[CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([OH:23])[CH:18]=2)[CH2:12][O:11][C@@H:10]([O:29][CH2:30][C:31]2([CH3:36])[CH2:35][CH2:34][CH2:33][CH2:32]2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[F:37][CH:38]([F:41])[CH2:39]Br.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C=O.C(OCC)(=O)C>[C:1]([O:5][C:6]([N:8]1[C@@H:13]([C@@H:14]([OH:28])[C@@H:15]([NH:24][C:25](=[O:27])[CH3:26])[CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([O:23][CH2:39][CH:38]([F:41])[F:37])[CH:18]=2)[CH2:12][O:11][C@@H:10]([O:29][CH2:30][C:31]2([CH3:36])[CH2:32][CH2:33][CH2:34][CH2:35]2)[CH2:9]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

参加物

6

反応物 3

HCID 10796Cesium carbonateHCID 1361862-Bromo-1,1-difluoroethaneHCID 68562669(2R,5R)-5-[(1S,2S)-2-Acetylamino-1-hydroxy-3-(3-hydroxyphenyl)-propyl]-2-(1-methylcyclopentylmethoxy)-morpholine-4-carboxylic acid tert-butyl ester

生成物 1

HCID 58972247(2R,5R)-5-{(1S,2S)-2-Acetylamino-3-[3-(2,2-difluoroethoxy)-phenyl]-1-hydroxypropyl}-2-(1-methylcyclopentylmethoxy)-morpholine-4-carboxylic acid tert-butyl ester

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
60 °C

実験手順

Dissolve (2R,5R)-5-[(1S,2S)-2-acetylamino-1-hydroxy-3-(3-hydroxyphenyl)-propyl]-2-(1-methylcyclopentylmethoxy)-morpholine-4-carboxylic acid tert-butyl ester (204 mg) and 2,2-difluoro-1-bromoethane (0.065 mL) and cesium carbonate (391 mg) in N,N-dimethylformamide (5 mL) and heat to 60° C. for 18 hours. Dilute with ethyl acetate, wash with saturated aqueous sodium chloride, dry and purify (silica gel chromatography, eluting with 1:1 ethyl acetate:dichloromethane), to give the desired compound (223 mg).

後処理

  1. washwash with saturated aqueous sodium chloride
  2. customdry
  3. custompurify
  4. wash(silica gel chromatography, eluting with 1:1 ethyl acetate:dichloromethane)

出典と根拠

ORDレコード
ord-50f5559b755c41c4bb23b87a638117e2
出典データセット
uspto-grants-2010_06
特許番号
US07745438B2

関連ノート

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