Ethanol → 1,1-Dimethylethyl N-((1S,2S)-3-chloro-2-hydroxy-1-(phenylmethyl)propyl)carbamate

HRID 2301739Notes

Reaction equation

HRID 2301739 reaction equation
C(OCC)(=O)C.C(O)C.[C:10]([O:14][C:15]([NH:17][C@@H:18]([CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[C:19](=[O:22])[CH2:20][Cl:21])=[O:16])([CH3:13])([CH3:12])[CH3:11].[BH4-].[Na+]>C(O)(=O)C>[C:10]([O:14][C:15]([NH:17][C@@H:18]([CH2:23][C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1)[C@H:19]([OH:22])[CH2:20][Cl:21])=[O:16])([CH3:13])([CH3:11])[CH3:12]

Participants

6

Reactant 4

HCID 702EthanolHCID 8857Ethyl AcetateHCID 4311764Sodium borohydrideHCID 9926241tert-butyl N-((2S)-4-chloro-3-oxo-1-phenylbutan-2-yl)carbamate

Product 1

HCID 71466451,1-Dimethylethyl N-((1S,2S)-3-chloro-2-hydroxy-1-(phenylmethyl)propyl)carbamateYield 72.6%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
60 °C

Procedure

Ethyl acetate (4.2 ml) and ethanol (16.7 ml) were added to (3S)-3-tert-butoxycarbonylamino-1-chloro-4-phenyl-2-butanone (2.08 g), and sodium borohydride (133 mg) was charged in divided portions at −10° C. The mixture was stirred for 1 hour and 40minutes. To the reaction solution was added acetic acid (0.40 ml) to terminate the reaction. The solution was heated at 60° C. over 1 hour, and further stirred at 60° C. for 30 minutes. Subsequently, the reaction solution was cooled to −10° C. over 1 hour and 50 minutes, and further stirred at −10° C. for 6 hours. Crystals obtained were collected by filtration, washed with water of 0° C., and dried under reduced pressure to obtain desired (2S,3S)-3-tert-butoxycarbonylamino-1-chloro-2-hydroxy-4-phenylbutane (1.52 g). The dry crystals were analyzed by HPLC, and found to be crystals having a quality of (2S,3S):(2R,3S)=98.5:1.5.

Workup

  1. additionwas charged in divided portions at −10° C
  2. customto terminate
  3. customthe reaction
  4. stirringfurther stirred at 60° C. for 30 minutes
  5. temperatureSubsequently, the reaction solution was cooled to −10° C. over 1 hour and 50 minutes
  6. stirringfurther stirred at −10° C. for 6 hours
  7. customCrystals obtained
  8. filtrationwere collected by filtration
  9. washwashed with water of 0° C.
  10. customdried under reduced pressure

Sources & evidence

ORD record
ord-cabc60def19948c99b7d9e310b9cebe4
Source dataset
uspto-grants-2002_12
Patent number
US06500985B2

Reaction notes

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