Sodium borohydride → HCID 118045554, compound

HRID 596037Notes

Reaction equation

HRID 596037 reaction equation
[NH2:1][C:2]1[C:3]([C:16]2[CH:28]=[CH:27][C:19]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])=[C:18]([F:29])[CH:17]=2)=[N:4][C:5]([C@@H:8]2[CH2:13][CH2:12][C:11](=[O:14])[C@@H:10]([F:15])[CH2:9]2)=[CH:6][N:7]=1.[BH4-].[Na+]>CO>[NH2:1][C:2]1[C:3]([C:16]2[CH:28]=[CH:27][C:19]([C:20]([O:22][C:23]([CH3:26])([CH3:24])[CH3:25])=[O:21])=[C:18]([F:29])[CH:17]=2)=[N:4][C:5]([C@@H:8]2[CH2:13][CH2:12][C@@H:11]([OH:14])[C@@H:10]([F:15])[CH2:9]2)=[CH:6][N:7]=1

Participants

4

Reactant 2

HCID 4311764Sodium borohydrideHCID 118054602HCID 118054602, compound

Product 1

HCID 118045554HCID 118045554, compoundYield 35.8%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of (+/−)-tert-butyl 4-(3-amino-6-((1R,3S)-3-fluoro-4-oxocyclohexyl)pyrazin-2-yl)-2-fluorobenzoate (208 mg, 0.516 mmol) in MeOH (3.017 mL) was added NaBH4 (29.3 mg, 0.773 mmol) at 0° C. The reaction mixture was stirred for 2 h. LCMS showed ˜4:1 ratio of two diastereomers. After quenched with NaHCO3 solution, the reaction mixture was extracted with EtOAc. The organic layer was washed with water and brine, dried over sodium sulfate, filtered off and concentrated in vacuo. The major diastereomer was separated by neutral prep HPLC. After lyophilzation, (+/−)-tert-butyl 4-(3-amino-6-((1R,3S,4R)-3-fluoro-4-hydroxycyclohexyl)pyrazin-2-yl)-2-fluorobenzoate was obtained in 35.8% yield. (74.9 mg). LCMS (m/z): 406.3 (MH+), 0.80 min. The relative stereochemistry of (+/−)-tert-butyl 4-(3-amino-6-((1R,3S,4R)-3-fluoro-4-hydroxycyclohexyl)pyrazin-2-yl)-2-fluorobenzoate was confirmed by NMR.

Workup

  1. customAfter quenched with NaHCO3 solution
  2. extractionthe reaction mixture was extracted with EtOAc
  3. washThe organic layer was washed with water and brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered off
  6. concentrationconcentrated in vacuo
  7. customThe major diastereomer was separated by neutral prep HPLC

Sources & evidence

ORD record
ord-78f6024111654b1b9d77e8a215fa2a2c
Source dataset
uspto-grants-2016_01
Patent number
US09242996B2

Reaction notes

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