Sodium Chloride → 3-Benzyloxycarbonylamino-3-(1,1-difluoro-2-hydroxy-ethyl)-piperidine-1-carboxylic acid tert-butyl ester

HRID 1912417Notes

Reaction equation

HRID 1912417 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][C:10]([NH:19][C:20]([O:22][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)=[O:21])([C:14]([F:18])([F:17])[CH:15]=C)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[O:30]=[O+][O-].[BH4-].[Na+].C(=O)(O)[O-].[Na+].[Cl-].[Na+]>C(Cl)(Cl)Cl.CO>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][C:10]([NH:19][C:20]([O:22][CH2:23][C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=2)=[O:21])([C:14]([F:17])([F:18])[CH2:15][OH:30])[CH2:9]1)=[O:7])([CH3:3])([CH3:4])[CH3:2]

Participants

7

Reactant 5

HCID 5234Sodium ChlorideHCID 24823OzoneHCID 516892Sodium BicarbonateHCID 4311764Sodium borohydrideHCID 582932963-Benzyloxycarbonylamino-3-(1,1-difluoro-allyl)-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 582933173-Benzyloxycarbonylamino-3-(1,1-difluoro-2-hydroxy-ethyl)-piperidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 21584188Chloroform methanolSolvent

Conditions

Temperature
0 °C

Procedure

A solution of an optically-active compound of 3-benzyloxycarbonylamino-3-(1,1-difluoro-allyl)-piperidine-1-carboxylic acid tert-butyl ester (15.1 g) in chloroform/methanol (150 ml/150 ml) cooled to −78° C. was flowed ozone air for 30 minutes. To the reaction mixture was added sodium borohydride (4.2 g) in small batches, and then the mixture was warmed to 0° C. and stirred at the same temperature for additional 50 minutes. To the mixture were added saturated aqueous sodium bicarbonate solution and saturated aqueous sodium chloride solution, and the mixture was extracted with chloroform. The separated aqueous layer was extracted with ethyl acetate. The combined organic layer was dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (eluent: n-hexane/ethyl acetate=3/1 to 2/1) to give the titled compound (13.6 g).

Workup

  1. customfor 30 minutes
  2. extractionthe mixture was extracted with chloroform
  3. extractionThe separated aqueous layer was extracted with ethyl acetate
  4. dry with materialThe combined organic layer was dried over anhydrous sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe resulting residue was purified by silica gel column chromatography (eluent: n-hexane/ethyl acetate=3/1 to 2/1)

Sources & evidence

ORD record
ord-2613eeb64b30461ebc4ed74c00c933db
Source dataset
uspto-grants-2013_12
Patent number
US08609647B2

Reaction notes

Loading…