Boron trifluoride etherate → HCID 86690118, compound

HRID 520408Notes

Reaction equation

HRID 520408 reaction equation
COCCN(S(F)(F)F)CCOC.B(F)(F)F.CCOCC.[C:23]([O:31][CH2:32][C@@:33]1([CH3:40])[CH2:38][C:37](=O)[CH2:36][CH2:35][O:34]1)(=[O:30])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.[FH:41].[FH:42].F.C(N(CC)CC)C.C[N+]1([O-])CCOCC1>C(Cl)Cl.CC(C)=O.CCOC(C)=O.[Os](=O)(=O)(=O)=O.O.C1COCC1>[C:23]([O:31][CH2:32][C@@:33]1([CH3:40])[CH2:38][C:37]([F:42])([F:41])[CH2:36][CH2:35][O:34]1)(=[O:30])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1

Participants

12

Reactant 5

HCID 8000Boron trifluoride etherateHCID 82029Methyl morpholine oxideHCID 175505N,N-Diethylethanamine trihydrofluorideHCID 2734690(Bis(2-methoxyethyl)amino)sulfur trifluoride2×HCID 86690119(2R)-2-[(Benzoyloxy)methyl]tetrahydro-2-methyl-4H-pyran-4-one

Product 1

HCID 86690118HCID 86690118, compoundYield 289.2%

Reagents, catalysts & solvents 6

HCID 30318Osmium TetroxideCatalystHCID 180AcetoneSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of Deoxo-Fluor® (1.5 mL, 8.14 mmol) in DCM (5 mL) was added boron trifluoride etherate (1 mL, 7.89 mmol) dropwise at 0° C. The mixture was stirred at rt for 1 h. A solution of (R)-(2-methyl-4-oxotetrahydro-2H-pyran-2-yl)methyl benzoate (0.7 g, 2.82 mmol) in DCM (5 mL) and triethylamine trihydrofluoride (0.1 mL, 0.614 mmol) were added dropwise in a 0° C. The reaction mixture was stirred at rt for 18 h and was recooled the reaction mixture in ice bath, added another portion of Deoxo-Fluor® (1 mL, 5.42 mmol) dropwise. The reaction mixture was stirred at rt for another 2 h. The reaction mixture was cautionly poured into a stirred ice cold aq. NaHCO3 solution and extracted with EtOAc (2×). The combined organic extraction was washed with NaHCO3, brine, dried (MgSO4), removed the solvent and purified on a 25 g silica gel cartridge (EtOAc/hex: 0 to 20%) to afford the product contaminated with vinyl by-product. The product was dissolved in acetone (4 mL), THF (16 mL), and added water (4 mL), NMO (0.330 g, 2.82 mmol) and osmium tetroxide (0.4 mL, 0.032 mmol) in ice bath. The reaction mixture was stirred at rt for 3 days and was diluted with EtOAc, washed with water, NH4Cl, brine, dried (MgSO4) and purified by silica gel flash chromatography to afford (R)-(4,4-difluoro-2-methyltetrahydro-2H-pyran-2-yl)methyl benzoate (0.48 g, 63%). 1H NMR (400 MHz, CHLOROFORM-d) ppm 8.13-8.04 (m, 2H), 7.60 (tt, J=7.4, 1.3 Hz, 1H), 7.52-7.39 (m, 2H), 4.42-4.34 (m, 1H), 4.24 (d, J=11.5 Hz, 1H), 4.00-3.84 (m, 2H), 2.21-1.93 (m, 4H), 1.46-1.36 (m, 3H).

Workup

  1. stirringThe reaction mixture was stirred at rt for 18 h
  2. stirringThe reaction mixture was stirred at rt for another 2 h
  3. extractionextracted with EtOAc (2×)
  4. extractionThe combined organic extraction
  5. washwas washed with NaHCO3, brine
  6. dry with materialdried (MgSO4)
  7. customremoved the solvent
  8. custompurified on a 25 g silica gel cartridge (EtOAc/hex: 0 to 20%)
  9. customto afford the product
  10. stirringThe reaction mixture was stirred at rt for 3 days
  11. washwashed with water, NH4Cl, brine
  12. dry with materialdried (MgSO4)
  13. custompurified by silica gel flash chromatography

Sources & evidence

ORD record
ord-a76199326f17496c8cc261103d024d4b
Source dataset
uspto-grants-2016_05
Patent number
US09326973B2

Reaction notes

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