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

HRID 1925856Notes

Reaction equation

HRID 1925856 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-ca8285ec03094d3580d303c392768f8b
Source dataset
uspto-grants-2012_05
Patent number
US08178693B2

Reaction notes

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