Acetone Cyanohydrin → 4-[4-(6-fluoro-5-methyl-2-oxo-1,3-benzoxazol-3(2H)-yl)-1-piperidinyl]tetrahydro-2H-pyran-4-carbonitrile

Temperature

70 °C

6-Fluoro-5-methyl-3-(4-piperidinyl)-1,3-benzoxazol-2(3H)-one (D3, 318 mg, 0.915 mmol) was dissolved in N,N-dimethylacetamide (10 mL) at rt under argon. Magnesium sulfate (562 mg, 4.67 mmol), acetone cyanohydrin (0.17 mL, 1.86 mmol) and tetrahydro-4H-pyran-4-one (0.17 mL, 1.84 mmol) were added and the reaction was heated at 70° C. for 24 h under a gentle stream of argon. The mixture was then cooled to rt, diluted with 1:1 dichloromethane:water (30 mL) and sonicated for 20 min. The phases were allowed to separate and the organic phase was dried by filtering through a hydrostatic cartridge. A further 10 mL of dichloromethane was added to the aqueous phase and the mixture stirred vigorously for 10 min. The 2 phases were again separated and the organic phase was dried by filtering through a hydrostatic cartridge. The combined organic layers were concentrated by rotary evaporation to give 4-[4-(6-fluoro-5-methyl-2-oxo-1,3-benzoxazol-3(2H)-yl)-1-piperidinyl]tetrahydro-2H-pyran-4-carbonitrile (D4, 681 mg, 45% purity, 93% yield) as an orange solid.

1. temperatureThe mixture was then cooled to rt
2. customto separate
3. customthe organic phase was dried
4. filtrationby filtering through a hydrostatic cartridge
5. additionA further 10 mL of dichloromethane was added to the aqueous phase
6. customThe 2 phases were again separated
7. customthe organic phase was dried
8. filtrationby filtering through a hydrostatic cartridge
9. concentrationThe combined organic layers were concentrated by rotary evaporation

ORD record

ord-b1d2e46f47e241aa80b217365ea70c5c

Source dataset

uspto-grants-2013_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08344000B2