Ethyl Acetate → tert-Butyl ((S)-2-(3,5-difluorophenyl)-1-((S)-oxiran-2-yl)ethyl)carbamate

HRID 1783194Notes

Reaction equation

HRID 1783194 reaction equation
Br[CH2:2][C@@H:3]([OH:22])[C@@H:4]([NH:14][C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])[CH2:5][C:6]1[CH:11]=[C:10]([F:12])[CH:9]=[C:8]([F:13])[CH:7]=1.C(OCC)(=O)C.[OH-].[K+]>C(O)C>[F:13][C:8]1[CH:7]=[C:6]([CH2:5][C@H:4]([NH:14][C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])[C@H:3]2[CH2:2][O:22]2)[CH:11]=[C:10]([F:12])[CH:9]=1

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 14797Potassium HydroxideHCID 57487171tert-Butyl (1S,2S)-3-bromo-1-(3,5-difluorobenzyl)-2-hydroxypropylcarbamate

Product 1

HCID 9922319tert-Butyl ((S)-2-(3,5-difluorophenyl)-1-((S)-oxiran-2-yl)ethyl)carbamate

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

tert-Butyl (1S, 2S)-3-bromo-1-(3,5-difluorobenzyl)-2-hydroxypropylcarbamate (IV, EXAMPLE 2) is dissolved in absolute alcohol (150 mL) and ethyl acetate (100 mL) and potassium hydroxide (2.3 g, 34.9 mmole, 1.1 eq.) in ethyl alcohol (85%, 5 mL) is added at −20 degrees C. The cold bath is then removed and the mixture stirred for 0.5 hour. The reaction is monitored by TLC (ethyl acetate/hexane, 20/80). When the reaction is complete, it is diluted with dichloromethane and extracted, washed with water, saline, dried over anhydrous sodium sulfate and the solvent removed under reduced pressure. The crude material is purified by flash chromatography on silica gel to give the title compound, TLC (ethyl acetate/hexane, 20/80) Rf=0.3; MS (MH+)=300.4.

Workup

  1. customThe cold bath is then removed
  2. additionit is diluted with dichloromethane
  3. extractionextracted
  4. washwashed with water, saline
  5. dry with materialdried over anhydrous sodium sulfate
  6. customthe solvent removed under reduced pressure
  7. customThe crude material is purified by flash chromatography on silica gel

Sources & evidence

ORD record
ord-873ccf4c46ea4fa28e13d81098c6543f
Source dataset
uspto-grants-2009_03
Patent number
US07498436B2

Reaction notes

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