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

Temperature

0 °C

EXAMPLE 306A (11.5 g) was dissolved in dichloromethane (40 mL) in a polypropylene bottle. The bottle was cooled to 0° C. To this mixture was added 70% hydrogen fluoride-pyridine (10.31 mL) slowly. The mixture 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 mixture 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% 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% HCl, brine
6. dry with materialdried (MgSO4)
7. filtrationfiltered
8. concentrationconcentrated

ORD record

ord-dae78d2f4fe2460da6a5bb2ec73d0b4c

Source dataset

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09315488B2