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

HRID 1936341Notes

Reaction equation

HRID 1936341 reaction equation
[CH3:1][O:2][C:3](=[O:24])/[C:4](/[C:11]1[CH:16]=[CH:15][C:14]([N:17]2[C:21]([CH3:22])=[N:20][N:19]=[N:18]2)=[C:13]([F:23])[CH:12]=1)=[CH:5]/[CH:6]1[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:24])[CH:4]([C:11]1[CH:16]=[CH:15][C:14]([N:17]2[C:21]([CH3:22])=[N:20][N:19]=[N:18]2)=[C:13]([F:23])[CH:12]=1)[CH2:5][CH:6]1[CH2:7][CH2:8][CH2:9][CH2:10]1

Participants

5

Reactant 2

HCID 4311764Sodium borohydrideHCID 69691984(E)-3-cyclopentyl-2-[3-fluoro-4-(5-methyl-tetrazol-1-yl)-phenyl]-acrylic acid methyl ester

Product 1

HCID 696918543-Cyclopentyl-2-[3-fluoro-4-(5-methyl-tetrazol-1-yl)-phenyl]-propionic acid methyl esterYield 99.5%

Reagents, catalysts & solvents 2

HCID 11791229Dichloronickel;hexahydrateCatalystHCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

A solution of nickel (II) chloride hexahydrate (115 mg, 0.24 mmol) and (E)-3-cyclopentyl-2-[3-fluoro-4-(5-methyl-tetrazol-1-yl)-phenyl]-acrylic acid methyl ester (400 mg, 1.21 mmol) in methanol (10 mL) was cooled to 0° C. and then treated with sodium borohydride (275 mg, 3.63 mmol) in two 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 reaction mixture was concentrated in vacuo, and the residue was diluted with a 3N aqueous hydrochloric acid solution (30 mL) and ethyl acetate (50 mL). The two layers were separated. The organic layer was washed with a saturated aqueous sodium chloride solution (1×50 mL), dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo to afford racemic 3-cyclopentyl-2-[3-fluoro-4-(5-methyl-tetrazol-1-yl)-phenyl]-propionic acid methyl ester (400 mg, 99%) as a viscous oil: EI-HRMS m/e calcd for C17H21FN4O2 (M+) 332.1648, found 332.1645.

Workup

  1. additionAfter the addition
  2. temperatureto warm to 25° C. where it
  3. stirringwas stirred for 15 h
  4. concentrationThe reaction mixture was concentrated in vacuo
  5. additionthe residue was diluted with a 3N aqueous hydrochloric acid solution (30 mL) and ethyl acetate (50 mL)
  6. customThe two layers were separated
  7. washThe organic layer was washed with a saturated aqueous sodium chloride solution (1×50 mL)
  8. dry with materialdried over anhydrous magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-35f432a06b7e451888078bd488ecf9d4
Source dataset
uspto-grants-2002_05
Patent number
US06388088B1

Reaction notes

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