Sodium Chloride → 3-Benzyloxycarbonylamino-3-(1,1-difluoro-2-hydroxyethyl)pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 1912409Notes

Reaction equation

HRID 1912409 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C:10]([NH:18][C:19]([O:21][CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=[O:20])([C:13]([F:17])([F:16])[CH:14]=C)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[O:29]=[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[CH2:12][CH2:11][C:10]([NH:18][C:19]([O:21][CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=[O:20])([C:13]([F:17])([F:16])[CH2:14][OH:29])[CH2:9]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

7

Reactant 5

HCID 5234Sodium ChlorideHCID 24823OzoneHCID 516892Sodium BicarbonateHCID 4311764Sodium borohydrideHCID 67223954HCID 67223954, compound

Product 1

HCID 672228133-Benzyloxycarbonylamino-3-(1,1-difluoro-2-hydroxyethyl)pyrrolidine-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-difluoroallyl)pyrrolidine-1-carboxylic acid tert-butyl ester (15.5 g) in chloroform/methanol (154 ml/154 ml) cooled to −78° C. was flowed ozone air for 30 minutes. To the reaction mixture was added sodium borohydride (4.14 g) in small batches, and then the mixture was warmed to 0° C. and stirred at the same temperature for additional 4 hours. 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). The fractions which could not be separated and isolated were concentrated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (eluent: n-hexane/chloroform/ethyl acetate=5/4/1) again. The purified fractions were combined and concentrated under reduced pressure to give the titled compound (12.8 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)
  7. customThe fractions which could not be separated
  8. customisolated
  9. concentrationwere concentrated under reduced pressure
  10. customthe resulting residue was purified by silica gel column chromatography (eluent: n-hexane/chloroform/ethyl acetate=5/4/1) again
  11. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-25c3416388ed4df7a2cba5036dae9d27
Source dataset
uspto-grants-2013_12
Patent number
US08609647B2

Reaction notes

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