Boron trifluoride etherate → HCID 68210982, compound

HRID 874753Notes

Reaction equation

HRID 874753 reaction equation
[C:1]([O:5][C:6](=[O:23])[NH:7][C@H:8]1[CH2:13][C:12](=[O:14])[CH2:11][O:10][C@@H:9]1[C:15]1[CH:20]=[C:19]([F:21])[CH:18]=[CH:17][C:16]=1[F:22])([CH3:4])([CH3:3])[CH3:2].B(F)(F)F.[CH3:28]COCC.C[Si](C=[N+]=[N-])(C)C.C1(C)C=CC(S([O-])(=O)=O)=CC=1.[NH+]1C=CC=CC=1>C(Cl)Cl.C(OCC)C.C([O-])(O)=O.[Na+].CO>[C:1]([O:5][C:6](=[O:23])[NH:7][C@H:8]1[CH2:13][C:12](=[O:14])[CH2:11][CH2:28][O:10][C@@H:9]1[C:15]1[CH:20]=[C:19]([F:21])[CH:18]=[CH:17][C:16]=1[F:22])([CH3:2])([CH3:4])[CH3:3]

Participants

9

Reactant 4

HCID 8000Boron trifluoride etherateHCID 167693TrimethylsilyldiazomethaneHCID 466102Benzenesulfonic acid, 4-methyl-, compd. with pyridine (1:1)HCID 441939251,1-Dimethylethyl N-[(2R,3S)-2-(2,5-difluorophenyl)tetrahydro-5-oxo-2H-pyran-3-yl]carbamate

Product 1

HCID 68210982HCID 68210982, compound

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent3×HCID 516892Sodium BicarbonateSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of tert-butyl[(2R,3S)-5-oxo-2-(2,5-difluorophenyl)tetrahydro-2H-pyran-3-yl]carbamate (Intermediate 2 in U.S. Pat. No. 7,678,905, the contents of which are herein incorporated by reference in their entirety) (6 g, 18.3 mmol) in DCM (185 mL) cooled to −78° C. was added boron trifluoride diethyl etherate (9.3 mL, 73.3 mmol) dropwise via syringe. After stirring 10 min at −78° C., trimethylsilyldiazomethane (11 mL, 22 mmol, 2 M in hexane) was added dropwise via syringe and the reaction was stirred 1.5 h at −78° C. The reaction mixture was diluted with diethyl ether and sat. aqueous NaHCO3, extracted with diethyl ether (×2) and the combined extracts were washed with brine, dried over Na2SO4, filtered and concentrated. The resulting oil was dissolved in a mixture of DCM (50 mL) and methanol (50 mL) and pyridiniump-toluenesulfonate (460 mg, 1.83 mmol) was added. The reaction was stirred 18 h at rt, then diluted with DCM and sat. aq. NaHCO3, washed with sat. aq. NaHCO3 and brine, then dried over Na2SO4, filtered and concentrated. The resulting oil was purified by column chromatography (100 g column, 8% to 70% EtOAc:Hex ramp) to provide the title compound as a white solid.

Workup

  1. stirringthe reaction was stirred 1.5 h at −78° C
  2. extractionextracted with diethyl ether (×2)
  3. washthe combined extracts were washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. additionwas added
  8. stirringThe reaction was stirred 18 h at rt
  9. washwashed with sat. aq. NaHCO3 and brine
  10. dry with materialdried over Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customThe resulting oil was purified by column chromatography (100 g column, 8% to 70% EtOAc:Hex ramp)

Sources & evidence

ORD record
ord-7e44653db42142ba932087ebdbb6d38d
Source dataset
uspto-grants-2015_03
Patent number
US08980929B2

Reaction notes

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