Sodium borohydride → [6-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3-(2-methanesulfonyl-ethyl)-3H-benzoimidazol-5-yl]-methanol

HRID 2104058Notes

Reaction equation

HRID 2104058 reaction equation
C[O:2][C:3]([C:5]1[C:19]([NH:20][C:21]2[CH:26]=[CH:25][C:24]([Br:27])=[CH:23][C:22]=2[Cl:28])=[C:18]([F:29])[C:8]2[N:9]=[CH:10][N:11]([CH2:12][CH2:13][S:14]([CH3:17])(=[O:16])=[O:15])[C:7]=2[CH:6]=1)=O.[BH4-].[Na+]>CCO.C1COCC1>[Br:27][C:24]1[CH:25]=[CH:26][C:21]([NH:20][C:19]2[C:5]([CH2:3][OH:2])=[CH:6][C:7]3[N:11]([CH2:12][CH2:13][S:14]([CH3:17])(=[O:16])=[O:15])[CH:10]=[N:9][C:8]=3[C:18]=2[F:29])=[C:22]([Cl:28])[CH:23]=1

Participants

5

Reactant 2

HCID 4311764Sodium borohydrideHCID 672515916-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3-(2-methanesulfonyl-ethyl)-3H-benzoimidazole-5-carboxylic acid methyl ester

Product 1

HCID 21114203[6-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3-(2-methanesulfonyl-ethyl)-3H-benzoimidazol-5-yl]-methanolYield 79.5%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

6-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3-(2-methanesulfonyl-ethyl)-3H-benzoimidazole-5-carboxylic acid methyl ester 11cc (0.300 g, 0.594 mmol) is suspended in a mixture of EtOH (6 mL) and THF (4 mL) under N2. NaBH4 (0.112 g, 2.97 mmol) is added. After approximately 4 days stirring, reaction mixture is quenched by the addition of AcOH until the reaction mixture reaches pH 7. The reaction mixture is concentrated to dryness under reduced pressure and the residue partitioned between ethyl acetate and water. The layers are separated and the organic layer is washed with water (3×), brine, and dried (Na2SO4). The organic layer is concentrated under reduced pressure until a white precipitate forms which is collected by filtration to give 0.225 g (79%) clean desired product: LC/MS ESI (+) m/z 478, 476 (M+ Br pattern) detected.

Workup

  1. customreaction mixture
  2. customis quenched by the addition of AcOH until the reaction mixture
  3. concentrationThe reaction mixture is concentrated to dryness under reduced pressure
  4. customthe residue partitioned between ethyl acetate and water
  5. customThe layers are separated
  6. washthe organic layer is washed with water (3×), brine
  7. dry with materialdried (Na2SO4)
  8. concentrationThe organic layer is concentrated under reduced pressure until a white precipitate forms which
  9. filtrationis collected by filtration

Sources & evidence

ORD record
ord-d5d64de4dae64acd8ed85742c6000ac7
Source dataset
uspto-grants-2009_08
Patent number
US07576114B2

Reaction notes

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