Sodium borohydride → (4-Fluorooxan-4-yl)methanol

Temperature

0 °C

Dissolve (4-fluorotetrahydropyran-4-yl)-hydroxyacetonitrile (4.4 g, 29.8 mmol) in 2-propanol (48 mL) and water (12 mL). Cool to 0° C. under a nitrogen atmosphere. Add sodium borohydride (1.2 g, 31.7 mmol) and allow the resulting mixture to slowly warm to room temperature over 5.5 hours. Quench with acetone and stir for 1 h. Concentrate the mixture to ⅓ volume and dilute with ethyl acetate. Wash the resulting organic solution with saturated aqueous sodium bicarbonate solution and saturated aqueous ammonium chloride solution (twice). Combine the aqueous washes and dilute with saturated aqueous sodium chloride solution and extract with ethyl acetate (twice). Add these extracts to the crude reaction mixture and wash the resulting solution with saturated aqueous sodium chloride solution, dry (magnesium sulfate), filter, concentrate and purify (silica gel chromatography, eluting with 0:100 to 1:1 ethyl acetate:hexanes) to give the desired compound as a yellow oil (740 mg, 18%).

1. temperatureto slowly warm to room temperature over 5.5 hours
2. customQuench with acetone
3. concentrationConcentrate the mixture
4. additiondilute with ethyl acetate
5. washWash the resulting organic solution with saturated aqueous sodium bicarbonate solution and saturated aqueous ammonium chloride solution (twice)
6. additionCombine the aqueous washes and dilute with saturated aqueous sodium chloride solution
7. extractionextract with ethyl acetate (twice)
8. additionAdd these extracts to the crude
9. customreaction mixture
10. washwash the resulting solution with saturated aqueous sodium chloride solution
11. dry with materialdry (magnesium sulfate)
12. filtrationfilter
13. concentrationconcentrate
14. custompurify
15. wash(silica gel chromatography, eluting with 0:100 to 1:1 ethyl acetate:hexanes)

ORD record

ord-104768d9d85649b782be2cbf29865b75

Source dataset

uspto-grants-2010_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07745438B2