Dimethylformamide → 2,4-Difluoro-3-(2-hydroxyethyl)benzaldehyde

2,2,6,6-Tetramethylpiperidine (5 mL) was added to a solution of butyllithium (1.6M in hexanes, 19 mL) in THF (25 mL) at −70° C. A solution of 2-(2,6-difluorophenyl)ethanol (example 45, step a) (1.6 g) in THF (25 mL) was added dropwise and the resulting mixture stirred for 2 h. DMF (3.9 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 (2×50 mL). The combined organics were washed with brine (100 mL), dried over magnesium sulphate, filtered and evaporated. The residue was purified by silica gel chromatography eluting with 4:1 to 2:1 isohexane:ether gradient. The fractions containing product were combined and evaporated. The resulting oil was dissolved in ethyl acetate (50 mL) and washed with HCl solution (2M, 30 mL), brine (30 mL), dried over magnesium sulphate, filtered and evaporated to give the subtitled compound as a clear oil. Yield 1.1 g.

1. stirringthe mixture stirred for 1 h at −70° C
2. stirringstirred for 70 h
3. customThe reaction was quenched with HCl solution (2M, 50 mL)
4. additiondiluted with ethyl acetate (100 mL)
5. customthe layers separated
6. extractionThe aqueous phase was extracted with ethyl acetate (2×50 mL)
7. washThe combined organics were washed with brine (100 mL)
8. dry with materialdried over magnesium sulphate
9. filtrationfiltered
10. customevaporated
11. customThe residue was purified by silica gel chromatography
12. washeluting with 4:1 to 2:1 isohexane
13. additionThe fractions containing product
14. customevaporated
15. dissolutionThe resulting oil was dissolved in ethyl acetate (50 mL)
16. washwashed with HCl solution (2M, 30 mL), brine (30 mL)
17. dry with materialdried over magnesium sulphate
18. filtrationfiltered
19. customevaporated

ORD record

ord-4cf0840f537145789058fb211a91ff41

Source dataset

uspto-grants-2012_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08148373B2