Potassium Carbonate → HCID 69537558, compound

HRID 1504805Notes

Reaction equation

HRID 1504805 reaction equation
Br[CH2:2][C:3](=[O:8])[C:4]([F:7])([F:6])[F:5].[BH4-].[Na+].[N-:11]=[N+]=[N-].[Na+].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[K+].[K+].[CH2:40]([O:47][C:48]([O:50]N1C(=O)CCC1=O)=O)[C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1>CO.ClCCl>[F:5][C:4]([F:7])([F:6])[CH:3]([OH:8])[CH2:2][NH:11][C:48](=[O:50])[O:47][CH2:40][C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1

Participants

9

Reactant 6

HCID 11430Potassium CarbonateHCID 11776TriphenylphosphineHCID 33557Sodium AzideHCID 790083-Bromo-1,1,1-trifluoro-2-propanoneHCID 83172Benzyl succinimido carbonateHCID 4311764Sodium borohydride

Product 1

HCID 69537558HCID 69537558, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of 3-bromo-1,1,1-trifluoropropan-2-one (150 g, 789 mmol) in methanol (600 mL) was added sodium borohydride (21 g, 550 mmol) in several batches at 0-5° C. over a period of 3 hours. After 2 hours post-addition, the reaction mixture was quenched with acetic acid (30 g). To this mixture was added dropwise sodium azide (5.22 M solution in water, 150 mL, 785 mmol). The reaction mixture was heated to 70° C. After 16 hours, the reaction mixture was cooled to ambient temperature, and triphenylphosphine (250 g, 954 mmol) was added. The reaction mixture was concentrated under reduced pressure, diluted with water (700 mL), and filtered. The filtrate was extracted with DCM (2×500 mL). To the combined organic layers were added potassium carbonate (2.0 g, 14 mmol) and N-(benzyloxycarbonyloxy)succinimide (1.76 M in acetone, 450 mL, 794 mmol). After 16 hours, the reaction mixture was diluted with dichloromethane (2400 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to afford the crude residue. The residue was purified via chromatography on silica gel (10-20% ethyl acetate/petroleum ether, linear gradient) to afford benzyl (3,3,3-trifluoro-2-hydroxypropyl)carbamate.

Workup

  1. additionAfter 2 hours post-addition
  2. customthe reaction mixture was quenched with acetic acid (30 g)
  3. temperaturethe reaction mixture was cooled to ambient temperature
  4. concentrationThe reaction mixture was concentrated under reduced pressure
  5. additiondiluted with water (700 mL)
  6. filtrationfiltered
  7. extractionThe filtrate was extracted with DCM (2×500 mL)
  8. waitAfter 16 hours
  9. dry with materialdried over anhydrous sodium sulfate
  10. concentrationconcentrated under reduced pressure
  11. customto afford the crude residue
  12. customThe residue was purified via chromatography on silica gel (10-20% ethyl acetate/petroleum ether, linear gradient)

Sources & evidence

ORD record
ord-41f5d643441d4da0bbb812d1d0bb9d85
Source dataset
uspto-grants-2015_12
Patent number
US09216173B2

Reaction notes

Loading…