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

HRID 430385Notes

Reaction equation

HRID 430385 reaction equation
[CH3:1][O:2][C:3](=[O:26])/[C:4](/[C:12]1[CH:17]=[CH:16][C:15]([S:18]([CH3:21])(=[O:20])=[O:19])=[C:14]([C:22]([F:25])([F:24])[F:23])[CH:13]=1)=[CH:5]/[CH:6]1[CH2:11][CH2:10][CH2:9][CH2:8][CH2:7]1.[BH4-].[Na+]>CO.O.O.O.O.O.O.[Ni](Cl)Cl>[CH3:1][O:2][C:3](=[O:26])[CH:4]([C:12]1[CH:17]=[CH:16][C:15]([S:18]([CH3:21])(=[O:19])=[O:20])=[C:14]([C:22]([F:25])([F:24])[F:23])[CH:13]=1)[CH2:5][CH:6]1[CH2:11][CH2:10][CH2:9][CH2:8][CH2:7]1

Participants

5

Reactant 2

HCID 4311764Sodium borohydrideHCID 67482950(E)-3-cyclohexyl-2-(4-methanesulfonyl-3-trifluoromethyl-phenyl)-acrylic acid methyl ester

Product 1

HCID 541116243-Cyclohexyl-2-(4-methanesulfonyl-3-trifluoromethyl-phenyl)-propionic acid methyl esterYield 93%

Reagents, catalysts & solvents 2

HCID 11791229Dichloronickel;hexahydrateCatalystHCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-190c94dc0a7a4e9a973b941354b12c5c
Source dataset
uspto-grants-2001_11
Patent number
US06320050B1

Reaction notes

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