Ethyl Acetate → 2-(4-fluorotetrahydro-2H-pyran-4-yl)-2-hydroxyacetonitrile

Temperature

0 °C

EXAMPLE 296A (11.5 g) was dissolved in dichloromethane (40 mL) in a polypropylene bottle. The bottle was cooled to 0° C. To this solution was added 70% hydrogen fluoride-pyridine (10.3 mL) slowly. The solution was allowed to warm to room temperature over 3 hours, and stirred for 24 hours. The reaction mixture was diluted with ethyl acetate (200 mL) and poured into saturated aqueous NaHCO3. Additional solid NaHCO3 was used to neutralize the solution carefully until bubbling ceased. The organic layer was isolated, and the aqueous layer was extracted with additional ethyl acetate three times (150 mL each). The combined organic layers were washed with 1% aqueous HCl, brine, dried (MgSO4), filtered and concentrated to give the desired compound which was used directly in the next reaction.

1. temperatureto warm to room temperature over 3 hours
2. customuntil bubbling
3. customThe organic layer was isolated
4. extractionthe aqueous layer was extracted with additional ethyl acetate three times (150 mL each)
5. washThe combined organic layers were washed with 1% aqueous HCl, brine
6. dry with materialdried (MgSO4)
7. filtrationfiltered
8. concentrationconcentrated

ORD record

ord-40b047a8309547eab7b8d3c9bfccc349

Source dataset

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08952157B2