(3,4-Difluorophenyl)acetic acid → 5-Chloro-2-(3,4-difluorophenyl)pentanoic acid

Temperature

0 °C

To a solution of 3,4-difluorophenylacetic acid (5.00 g, 29.0 mmol) in THF (58 mL) was added NaHMDS (1 M in THF, 58.1 mL, 58.1 mmol) dropwise at 0° C. The reaction mixture was then stirred at 0° C. for 20 min, then 1-chloro-3-iodopropane (3.12 mL, 29.0 mmol) was added dropwise at 0° C. and the reaction mixture was stirred at room temperature for 16 hours. The mixture was then quenched under ice bath cooling with water (3 mL) and evaporated. To the residue was added NaOH (1 N, 150 mL) and the resulting solution was extracted with diethylether (2×100 mL). The aqueous layer was acidified with HCl (1 N, 200 mL) and extracted with diethylether (2×100 mL). The combined organic layers were then dried over sodium sulfate, filtered and evaporated. Purification by chromatography (silica gel, 2×50 g, 0 to 50% ethyl acetate in heptane) afforded the title compound (2.02 g, 28%) as a light yellow oil.

1. stirringthe reaction mixture was stirred at room temperature for 16 hours
2. customThe mixture was then quenched under ice bath
3. temperaturecooling with water (3 mL)
4. customevaporated
5. additionTo the residue was added NaOH (1 N, 150 mL)
6. extractionthe resulting solution was extracted with diethylether (2×100 mL)
7. extractionextracted with diethylether (2×100 mL)
8. dry with materialThe combined organic layers were then dried over sodium sulfate
9. filtrationfiltered
10. customevaporated
11. customPurification by chromatography (silica gel, 2×50 g, 0 to 50% ethyl acetate in heptane)

ORD record

ord-a72462bac1a64125852baed846b2ec85

Source dataset

uspto-grants-2013_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08486967B2