Dimethylformamide → 2-Fluoro-3-(2-hydroxyethyl)benzaldehyde

Temperature

-70 °C

2,2,6,6-Tetramethylpiperidine (10.8 mL) was added to a solution of butyllithium (1.6M in hexanes, 40.1 mL) in THF (40 mL) at −70° C. A solution of 2-(2-fluorophenyl)ethanol (3 g) in THF (40 mL) was added dropwise and the resulting mixture stirred for 6 h at −70° C. DMF (8.29 mL) was then added and the mixture stirred for 1 h at −70° C. The mixture was then allowed to warm to RT and stirred for 70 h. The reaction was quenched with HCl solution (2M, 50 mL), diluted with ethyl acetate (100 mL) and the layers separated. The aqueous phase was extracted with ethyl acetate (2×100 mL). The combined organic solutions were washed with HCl solution (2M, 50 mL), brine (20 mL), dried over magnesium sulphate, filtered and evaporated. The residue was purified by silica gel chromatography eluting with 4:1 to 2:1 isohexane:ethyl acetate gradient. The fractions containing product were combined and evaporated to give the subtitled compound as a yellow oil. Yield 1.2 g.

1. stirringthe mixture stirred for 1 h at −70° C
2. temperatureto warm to RT
3. stirringstirred for 70 h
4. customThe reaction was quenched with HCl solution (2M, 50 mL)
5. additiondiluted with ethyl acetate (100 mL)
6. customthe layers separated
7. extractionThe aqueous phase was extracted with ethyl acetate (2×100 mL)
8. washThe combined organic solutions were washed with HCl solution (2M, 50 mL), brine (20 mL)
9. dry with materialdried over magnesium sulphate
10. filtrationfiltered
11. customevaporated
12. customThe residue was purified by silica gel chromatography
13. washeluting with 4:1 to 2:1 isohexane
14. additionThe fractions containing product
15. customevaporated

ORD record

ord-5b4e5db3e3114d65ac15c63e3a288d0d

Source dataset

uspto-grants-2014_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08629271B2