Sodium hydride → (S)-2-[5-Bromo-2-oxo-3-(4-trifluoromethylbenzoylamino)-2H-pyridin-1-yl]-3-phenylpropionic acid methyl ester

To a solution of N-(5-bromo-2-hydroxypyridin-3-yl)-4-trifluoromethyl-benzamide from Step D (760 mg, 2.1 mmol) in tetrahydrofuran (10 mL) was added 95% sodium hydride (80 mg, 3.15 mmol) at room temperature. After the reaction mixture was stirred at room temperature for 30 min, (R)-2-methanesulfonyloxy-3-phenylpropionic acid methyl ester from Step B (820 mg, 3.15 mmol) was added and the reaction was stirred and heated at 50° C. for 20 h. The reaction mixture was cooled to room temperature and diluted with ethyl acetate (100 mL) and washed with saturated ammonium chloride solution and brine. The organic layer was separated, dried with sodium sulfate, filtered and concentrated in vacuo. Purification by medium pressure liquid chromatography on silica gel (1:6 ethyl acetate/hexanes) gave 770 mg (70%) of the title compound as a semisolid.

1. stirringthe reaction was stirred
2. temperatureheated at 50° C. for 20 h
3. temperatureThe reaction mixture was cooled to room temperature
4. washwashed with saturated ammonium chloride solution and brine
5. customThe organic layer was separated
6. dry with materialdried with sodium sulfate
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. customPurification by medium pressure liquid chromatography on silica gel (1:6 ethyl acetate/hexanes)

ORD record

ord-5d20f741e39649beb44e6c36ba4af93d

Source dataset

uspto-grants-2006_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07087622B2