Ozone → [1-(2-Fluoro-phenyl)-3-hydroxy-1-trifluoromethyl-propyl]-carbamic acid tert-butyl ester

HRID 221762Notes

Reaction equation

HRID 221762 reaction equation
[C:1]([O:5][C:6](=[O:23])[NH:7][C:8]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[F:22])([C:12]([F:15])([F:14])[F:13])[CH2:9][CH:10]=C)([CH3:4])([CH3:3])[CH3:2].C([O-])(O)=[O:25].[Na+].O=[O+][O-].[BH4-].[Na+]>C(Cl)Cl.CO.O=O>[C:1]([O:5][C:6](=[O:23])[NH:7][C:8]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[F:22])([C:12]([F:15])([F:14])[F:13])[CH2:9][CH2:10][OH:25])([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 4

HCID 24823OzoneHCID 516892Sodium BicarbonateHCID 4311764Sodium borohydrideHCID 66666093[1-(2-Fluoro-phenyl)-1-trifluoromethyl-but-3-enyl]-carbamic acid tert-butyl ester

Product 1

HCID 66849443[1-(2-Fluoro-phenyl)-3-hydroxy-1-trifluoromethyl-propyl]-carbamic acid tert-butyl esterYield 83.5%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 977OxygenSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
-75 °C

Procedure

A suspension of [[1-(2-fluoro-phenyl)-1-trifluoromethyl-but-3-enyl]-carbamic acid tert-butyl ester (9.27 g, 27.8 mmol) and NaHCO3 (3.50 g, 41.7 mmol) in 168 ml DCM and 56 ml MeOH was cooled to −75° C. A mixture of O3 in oxygen gas was introduced till the blue color persisted. The excess ozone was removed by bubbling through oxygen gas for 10 minutes. Solid NaBH4 (2.10 g, 55.6 mmol) was added in two portions. The mixture was stirred 10 min at −75° C. and then allowed to warm to 0° C. After 30 minutes, the mixture was poured onto ice-cold 1N HCl and extracted with TBME. The organic phase is washed with 1N HCl, brine, dried with MgSO4.H2O and evaporated. Crystallization from hexane provided 7.83 g of the title compound as white crystals.

Workup

  1. additionwas introduced till the blue color
  2. customThe excess ozone was removed
  3. customby bubbling through oxygen gas for 10 minutes
  4. temperatureto warm to 0° C
  5. waitAfter 30 minutes
  6. additionthe mixture was poured onto ice-cold 1N HCl
  7. extractionextracted with TBME
  8. washThe organic phase is washed with 1N HCl, brine
  9. dry with materialdried with MgSO4.H2O
  10. customevaporated
  11. customCrystallization from hexane

Sources & evidence

ORD record
ord-7f55594476b44bf791d24feba3818c14
Source dataset
uspto-grants-2012_06
Patent number
US08207164B2

Reaction notes

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