Methanesulfonyl chloride → methanesulfonic acid (S)-2-(4-bromo-2-methoxy-phenyl)-4-tert-butoxycarbonylamino-butyl ester

HRID 503923ノート

反応式

HRID 503923 の反応式
[S:1](Cl)([CH3:4])(=[O:3])=[O:2].[C:6]([O:10][C:11](=[O:27])[NH:12][CH2:13][CH2:14][C@@H:15]([C:18]1[CH:23]=[CH:22][C:21]([Br:24])=[CH:20][C:19]=1[O:25][CH3:26])[CH2:16][OH:17])([CH3:9])([CH3:8])[CH3:7].C([O-])(O)=O.[Na+]>C(Cl)Cl>[Br:24][C:21]1[CH:22]=[CH:23][C:18]([C@H:15]([CH2:14][CH2:13][NH:12][C:11]([O:10][C:6]([CH3:9])([CH3:8])[CH3:7])=[O:27])[CH2:16][O:17][S:1]([CH3:4])(=[O:3])=[O:2])=[C:19]([O:25][CH3:26])[CH:20]=1

参加物

5

反応物 3

HCID 31297Methanesulfonyl chlorideHCID 516892Sodium BicarbonateHCID 66877031[(S)-3-(4-bromo-2-methoxy-phenyl)-4-hydroxy-butyl]-carbamic acid tert-butyl ester

生成物 1

HCID 86621499methanesulfonic acid (S)-2-(4-bromo-2-methoxy-phenyl)-4-tert-butoxycarbonylamino-butyl ester収率 100.8%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

反応条件

温度
-78 °C

実験手順

Mesyl chloride (93.7 μL, 1.21 mmol) was added to a solution of [(S)-3-(4-bromo-2-methoxy-phenyl)-4-hydroxy-butyl]-carbamic acid tert-butyl ester (394 mg, 1.0527 mmol) in DCM (7.5 mL) under argon atmosphere at −78° C., followed by addition of TEA (0.336 mL, 2.42 mmol). The mixture was stirred at −78° C. for 1 hour and then at room temperature for an additional hour. A solution of aqueous NaHCO3 (10%) was added, and the organic layer was separated and dried over Na2SO4. Solvent was evaporated under reduced pressure and to afford 480 mg of crude methanesulfonic acid (S)-2-(4-bromo-2-methoxy-phenyl)-4-tert-butoxycarbonylamino-butyl ester. This material was dissolved in THF (4 mL) under Ar atmosphere and cooled to 0° C. KHMDS (0.5 M in toluene, 2.32 mL, 1.158 mmol) was added, and the reaction mixture was stirred for 1 hour at room temperature. A saturated solution of NH4Cl was added, followed by brine, and the resulting mixture was extracted with EtOAc. The combined organic extracts were washed with brine, dried over Na2SO4, filtered, and evaporated under reduced pressure. The residue was purified via flash chromatography (hexane/EtOAc, 98/2) to give 315 mg (84% yield) of (S)-3-(4-bromo-2-methoxy-phenyl)-pyrrolidine-1-carboxylic acid tert-butyl ester in 99% ee determined by chiralcel HPLC column and hexane/i-PrOH (9/1) as mobile phase.

後処理

  1. waitat room temperature for an additional hour
  2. customthe organic layer was separated
  3. dry with materialdried over Na2SO4
  4. customSolvent was evaporated under reduced pressure

出典と根拠

ORDレコード
ord-6b2216725b094edf8788ff9ba383838a
出典データセット
uspto-grants-2010_08
特許番号
US07776910B2

反応ノート

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