Hydrochloric Acid → 4-[(2-chloro-4-fluorophenyl)hydroxymethyl]-5-(2,6-difluorophenyl)-1-methyl-1H-pyrazole-3-carbonitrile

HRID 406600Notes

Reaction equation

HRID 406600 reaction equation
[Cl:1][C:2]1[CH:25]=[C:24]([F:26])[CH:23]=[CH:22][C:3]=1[C:4]([C:6]1[C:7]([C:20]#[N:21])=[N:8][N:9]([CH3:19])[C:10]=1[C:11]1[C:16]([F:17])=[CH:15][CH:14]=[CH:13][C:12]=1[F:18])=[O:5].[BH4-].[Na+].Cl>C(O)C>[Cl:1][C:2]1[CH:25]=[C:24]([F:26])[CH:23]=[CH:22][C:3]=1[CH:4]([OH:5])[C:6]1[C:7]([C:20]#[N:21])=[N:8][N:9]([CH3:19])[C:10]=1[C:11]1[C:12]([F:18])=[CH:13][CH:14]=[CH:15][C:16]=1[F:17]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 4311764Sodium borohydrideHCID 666124294-(2-chloro-4-fluorobenzoyl)-5-(2,6-difluorophenyl)-1-methyl-1H-pyrazole-3-carbonitrile

Product 1

HCID 666139644-[(2-chloro-4-fluorophenyl)hydroxymethyl]-5-(2,6-difluorophenyl)-1-methyl-1H-pyrazole-3-carbonitrile

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a mixture of 4-(2-chloro-4-fluorobenzoyl)-5-(2,6-difluorophenyl)-1-methyl-1H-pyrazole-3-carbonitrile (i.e. the product of Example 10) (0.05 g, 0.13 mmol) in ethanol (2 mL) was added sodium borohydride (0.005 g, 0.13 mmol). The reaction was stirred for 30 minutes, and then hydrochloric acid (1 N) (0.5 mL) was added and the mixture was concentrated under reduced pressure. The resulting material was diluted with methylene chloride (5 mL) and filter through a Celite® (diatomaceous earth) extraction tube rinsing with methylene chloride (15 mL). The filtrate was concentrated under reduced pressure and the resulting material purified by flash chromatography on a silica gel, Varian Bond Elute SI® column (10 to 50% gradient of ethyl acetate in hexanes as eluant) to provide the title compound, a compound of the present invention, as a solid (0.03 g).

Workup

  1. concentrationthe mixture was concentrated under reduced pressure
  2. additionThe resulting material was diluted with methylene chloride (5 mL)
  3. filtrationfilter through a Celite® (diatomaceous earth) extraction tube
  4. washrinsing with methylene chloride (15 mL)
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. customthe resulting material purified by flash chromatography on a silica gel, Varian Bond
  7. washElute SI® column (10 to 50% gradient of ethyl acetate in hexanes as eluant)

Sources & evidence

ORD record
ord-65f12851405f4d0b9e148ce32c09d737
Source dataset
uspto-grants-2014_06
Patent number
US08754115B2

Reaction notes

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