Hydrochloric Acid → 2,3-Difluoro-5-(2-hydroxyethyl)benzaldehyde

Temperature

-70 °C

2,2,6,6-Tetramethylpiperidine (6.15 mL) was added to a solution of n-butyllithium in hexanes (1.6M, 22.8 mL) at −70° C. A solution of 2-(3,4-difluorophenyl)ethanol (example 32, step a) (1.92 g) in THF (25 mL) was added dropwise. THF (25 mL) was added and the mixture stirred at −70° C. for 6 h. DMF (4.7 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. Aqueous HCl solution (2M, 10 mL) was added followed by ethyl acetate (20 mL) and the layers separated. The aqueous phase was extracted with ethyl acetate (2×20 mL). The combined organic solutions were washed with brine (20 mL), dried over magnesium sulphate, filtered and evaporated in vacuo. Purification was by silica gel chromatography eluting with 4:1 to 2:1 isohexane:diethyl ether gradient. The fractions containing product were combined and evaporated in vacuo to give the subtitled compound as a yellow oil. Yield 1.9 g.

1. stirringthe mixture stirred for 1 h at −70° C
2. temperatureto warm to RT
3. stirringstirred for 70 h
4. customthe layers separated
5. extractionThe aqueous phase was extracted with ethyl acetate (2×20 mL)
6. washThe combined organic solutions were washed with brine (20 mL)
7. dry with materialdried over magnesium sulphate
8. filtrationfiltered
9. customevaporated in vacuo
10. customPurification
11. washeluting with 4:1 to 2:1 isohexane
12. additionThe fractions containing product
13. customevaporated in vacuo

ORD record

ord-68163201d840445ba655c4e744aeec76

Source dataset

uspto-grants-2012_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08148373B2