Sodium borohydride → 2-[3-Chloro-4-(5-trifluoromethyl-tetrazol-1-yl)-phenyl]-3-cyclohexyl-propionic acid methyl ester

Temperature

0 °C

A solution of nickel (II) chloride hexahydrate (77 mg, 0.324 mmol) and (E)-2-[3-chloro-4-(5-trifluoromethyl-tetrazol-1-yl)-phenyl]-3-cyclohexyl-acrylic acid methyl ester (674 mg, 1.62 mmol) in methanol (15 mL) was cooled to 0° C. and then treated with sodium borohydride (184 mg, 4.86 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 20 h. The reaction mixture was then concentrated in vacuo, and the residue was diluted with water (50 mL) and ethyl acetate (100 mL). The two layers were separated. 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 2-[3-chloro-4-(5-trifluoromethyl-tetrazol-1-yl)-phenyl]-3-cyclohexyl-propionic acid methyl ester (640 mg, 95%) as a viscous oil: EI-HRMS m/e calcd for C18H20ClF3N4O2 (M+) 416.1527, found 416.1529.

1. additionAfter the addition
2. temperatureto warm to 25° C. where it
3. stirringwas stirred for 20 h
4. concentrationThe reaction mixture was then concentrated in vacuo
5. additionthe residue was diluted with water (50 mL) and ethyl acetate (100 mL)
6. customThe two layers were separated
7. washThe organic layer was washed successively with a 3N aqueous hydrochloric acid solution (1×50 mL)
8. 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
9. filtrationfiltered
10. concentrationconcentrated in vacuo

ORD record

ord-16fc5f6e65ca4a6f851c62309ddf8875

Source dataset

uspto-grants-2002_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06369232B1