Methyl iodide → [(3S,4R)-1-Benzyl-4-(4-chloro-3-fluoro-phenyl)-pyrrolidin-3-yl]-methyl-carbamic acid tert-butyl ester

HRID 587407ノート

反応式

HRID 587407 の反応式
[C:1]([O:5][C:6](=[O:28])[NH:7][C@H:8]1[C@H:12]([C:13]2[CH:18]=[CH:17][C:16]([Cl:19])=[C:15]([F:20])[CH:14]=2)[CH2:11][N:10]([CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].I[CH3:32]>CN(C=O)C>[C:1]([O:5][C:6](=[O:28])[N:7]([C@H:8]1[C@H:12]([C:13]2[CH:18]=[CH:17][C:16]([Cl:19])=[C:15]([F:20])[CH:14]=2)[CH2:11][N:10]([CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH2:9]1)[CH3:32])([CH3:4])([CH3:2])[CH3:3]

参加物

5

反応物 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 58303063[(3S,4R)-1-Benzyl-4-(4-chloro-3-fluoro-phenyl)-pyrrolidin-3-yl]-carbamic acid tert-butyl ester

生成物 1

HCID 58303101[(3S,4R)-1-Benzyl-4-(4-chloro-3-fluoro-phenyl)-pyrrolidin-3-yl]-methyl-carbamic acid tert-butyl ester

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒2 回

反応条件

温度
60 °C

実験手順

A mixture of 5.7 g (14.1 mmol) [(3S,4R)-1-Benzyl-4-(4-chloro-3-fluoro-phenyl)-pyrrolidin-3-yl]-carbamic acid tert-butyl ester, 676 mg (17 mmol) NaH (55%) in DMF was stirred for 20 minutes at room temperature and 1 h at 60° C. 3 g (21 mmol) iodomethane in DMF was added and the mixture was stirred at 60° C. for 1 h and evaporated. The residue was taken up in ethyl acetate and water, the organic layer washed with brine and back-extracted with ethyl acetate. The combined organic layers were dried with Na2SO4, filtered off and evaporated. The residue was taken up on isolute and subjected to column chromatography on silica eluting with a gradient formed from ethyl acetate and heptane to yield after evaporation of the product containing fractions 2.67 g (45%) of the title compound as light yellow oil. MS m/e: 419.2 [M+H]+.

後処理

  1. stirringthe mixture was stirred at 60° C. for 1 h
  2. customevaporated
  3. washwater, the organic layer washed with brine
  4. extractionback-extracted with ethyl acetate
  5. dry with materialThe combined organic layers were dried with Na2SO4
  6. filtrationfiltered off
  7. customevaporated
  8. customformed from ethyl acetate and heptane
  9. customto yield
  10. customafter evaporation of the product
  11. additioncontaining fractions 2.67 g (45%) of the title compound as light yellow oil

出典と根拠

ORDレコード
ord-2d827ed3da7b4d55bfb622c0d9f30c1b
出典データセット
uspto-grants-2016_01
特許番号
US09226916B2

反応ノート

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