Sodium borohydride → (S)-N-(1-Ethyl-3-methyl-1H-pyrazol-4-yl)-2-hydroxy-2-phenyl-N-[2-(6-trifluoromethyl-pyridin-3-yl)-ethyl]-acetamide

HRID 1094394Notes

Reaction equation

HRID 1094394 reaction equation
[CH2:1]([N:3]1[CH:7]=[C:6]([N:8]([CH2:19][CH2:20][C:21]2[CH:22]=[N:23][C:24]([C:27]([F:30])([F:29])[F:28])=[CH:25][CH:26]=2)[C:9](=[O:18])[C:10](=[O:17])[C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[C:5]([CH3:31])=[N:4]1)[CH3:2].[BH4-].[Na+]>CO>[CH2:1]([N:3]1[CH:7]=[C:6]([N:8]([CH2:19][CH2:20][C:21]2[CH:22]=[N:23][C:24]([C:27]([F:30])([F:28])[F:29])=[CH:25][CH:26]=2)[C:9](=[O:18])[C@@H:10]([OH:17])[C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:5]([CH3:31])=[N:4]1)[CH3:2]

Participants

4

Reactant 2

HCID 4311764Sodium borohydrideHCID 58007515N-(1-Ethyl-3-methyl-1H-pyrazol-4-yl)-2-oxo-2-phenyl-N-[2-(6-trifluoromethyl-pyridin-3-yl)-ethyl]-acetamide

Product 1

HCID 58007581(S)-N-(1-Ethyl-3-methyl-1H-pyrazol-4-yl)-2-hydroxy-2-phenyl-N-[2-(6-trifluoromethyl-pyridin-3-yl)-ethyl]-acetamideYield 115.6%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

A solution of N-(1-ethyl-3-methyl-1H-pyrazol-4-yl)-2-oxo-2-phenyl-N-[2-(6-trifluoromethyl-pyridin-3-yl)-ethyl]-acetamide (145 mg, 0.34 mmol) was dissolved in MeOH (4 mL), cooled to 0° C. and treated with NaBH4 (38 mg, 1 mmol) and stirred for 12 h at ambient temperature. The reaction mixture was quenched with aqueous K2CO3 (2 M, 1 mL), concentrated, then redissolved in EtOAc (15 mL) and washed with aqueous K2CO3 (2 M, 3×15 mL). The combined aqueous layers were extracted with EtOAc (3×15 mL) and the combined organic layers dried over sodium sulfate. Concentration afforded the racemic compound (170 mg, >100%) as a light yellow oil. Separation by chromatography on a chiral column provided the title compound as a colourless oil (38 mg, 26%) MS m/e: 433.2 [M+H]+ which crystallized upon standing.

Workup

  1. customThe reaction mixture was quenched with aqueous K2CO3 (2 M, 1 mL)
  2. concentrationconcentrated
  3. dissolutionredissolved in EtOAc (15 mL)
  4. washwashed with aqueous K2CO3 (2 M, 3×15 mL)
  5. extractionThe combined aqueous layers were extracted with EtOAc (3×15 mL)
  6. dry with materialthe combined organic layers dried over sodium sulfate
  7. concentrationConcentration

Sources & evidence

ORD record
ord-3b6b6183be6647f8907c87917c80c47f
Source dataset
uspto-grants-2012_03
Patent number
US08133909B2

Reaction notes

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