Ammonium Chloride → (2S)-2-Isopropyl-2-hydroxy-3-(2-fluorophenyl)propanoic acid

Temperature

-78 °C

A solution of (o-fluorobenzyl)magnesium bromide in diethyl ether (100 mL), prepared from the corresponding o-fluorobenzyl bromide (9.45 g, 50.0 mmol) and magnesium turnings (1.32 g, 55.0 mmol), was added to a solution of ethyl 3-methyl-2-oxobutanoate (7.2 g, 50 mmol) in diethyl ether (50 mL) cooled at −78° C. After 30 min at −78° C., the reaction mixture was warmed to 0° C. and poured into saturated aqueous NH4Cl. The organic layer was washed with brine, dried and concentrated. The residue was dissolved in methanol (200 mL) and kept with 2 N KOH (75 mL) for 2 hrs. at 50° C. The reaction mixture was diluted with water and washed with hexane. The aqueous layer was acidified with 2 N HCl, saturated with sodium chloride and extracted with ethyl acetate. Removal of solvents gave the title compound.

1. temperaturethe reaction mixture was warmed to 0° C.
2. washThe organic layer was washed with brine
3. customdried
4. concentrationconcentrated
5. dissolutionThe residue was dissolved in methanol (200 mL)
6. waitkept with 2 N KOH (75 mL) for 2 hrs
7. customat 50° C
8. additionThe reaction mixture was diluted with water
9. washwashed with hexane
10. extractionextracted with ethyl acetate
11. customRemoval of solvents

ORD record

ord-48af04e53dfd42dc85cfc6e1748b0378

Source dataset

uspto-grants-2009_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07629372B2