Sodium borohydride → 3-Cyclohexyl-2-(4-methanesulfonyl-3-trifluoromethyl-phenyl)-propionic acid methyl ester

Temperature

0 °C

A solution of nickel(II) chloride hexahydrate (36.6 mg, 0.154 mmol) and (E)-3-cyclohexyl-2-(4-methanesulfonyl-3-trifluoromethyl-phenyl)-acrylic acid methyl ester (302 mg, 0.77 mmol) in methanol (8 mL) was cooled to 0° C. and then treated with sodium borohydride (87 mg, 2.29 mmol) in four portions. After the addition, the black reaction mixture was stirred for 15 min at 0° C. and then allowed to warm to 25° C. where it was stirred for 15 h. The black solid was filtered using filter paper and washed with methanol. The combined solvents were concentrated in vacuo, and the residue was diluted with ethyl acetate (50 mL). The organic layer was washed successively with a 3N aqueous hydrochloric acid solution (1×50 mL), a saturated aqueous sodium bicarbonate solution (1×50 mL) and a saturated aqueous sodium chloride solution (1×50 mL), dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo to afford racemic 3-cyclohexyl-2-(4-methanesulfonyl-3-trifluoromethyl-phenyl)-propionic acid methyl ester (280 mg, 93%) as a viscous oil: EI-HRMS m/e calcd for C18H23F3O4S (M+) 392.1269, found 392.1276.

1. additionAfter the addition
2. temperatureto warm to 25° C. where it
3. stirringwas stirred for 15 h
4. filtrationThe black solid was filtered
5. filtrationusing filter paper
6. washwashed with methanol
7. concentrationThe combined solvents were concentrated in vacuo
8. additionthe residue was diluted with ethyl acetate (50 mL)
9. washThe organic layer was washed successively with a 3N aqueous hydrochloric acid solution (1×50 mL)
10. dry with materiala saturated aqueous sodium bicarbonate solution (1×50 mL) and a saturated aqueous sodium chloride solution (1×50 mL), dried over anhydrous magnesium sulfate
11. filtrationfiltered
12. concentrationconcentrated in vacuo

ORD record

ord-5d74ee9ced7b44d1bb2c790c68dd5948

Source dataset

uspto-grants-2007_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07223868B2