Ammonium Chloride → (5-Bromo-2-chlorophenyl)-(1-phenylpyrazol-4-yl)methanol

HRID 1514610Notes

Reaction equation

HRID 1514610 reaction equation
[C:1]1([N:7]2[CH:11]=[C:10](Br)[CH:9]=[N:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C([Li])CCC.[Br:18][C:19]1[CH:20]=[CH:21][C:22]([Cl:27])=[C:23]([CH:26]=1)[CH:24]=[O:25].[Cl-].[NH4+]>C(OCC)C.O1CCCC1>[Br:18][C:19]1[CH:20]=[CH:21][C:22]([Cl:27])=[C:23]([CH:24]([C:10]2[CH:9]=[N:8][N:7]([C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)[CH:11]=2)[OH:25])[CH:26]=1

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 7868114-Bromo-1-phenyl-1H-pyrazoleHCID 106089255-Bromo-2-chlorobenzaldehydeHCID 178418339Butyllithium

Product 1

HCID 46930334(5-Bromo-2-chlorophenyl)-(1-phenylpyrazol-4-yl)methanol

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 1-phenyl-4-bromopyrazole (see M. A. Khan, et al., Can. J. Chem., (1963) 41 1540) (2.23 g) in diethyl ether (30 ml) wad cooled to −78° C. under argon atmosphere, and added dropwise thereto was n-butyl lithium (1.59 M hexane solution, 6.9 ml). The mixture was stirred at −20° C. to −10° C. for 5 hours, and added dropwise thereto at the same temperature was a solution of 5-bromo-2-chlorobenzaldehyde (2.19 g) obtained in Reference Example 16-(1) in diethyl ether (30 ml). The mixture was stirred at the same temperature for 30 minutes, and added thereto was tetrahydrofuran (30 ml), and the mixture was stirred at 0° C. for further 30 minutes. A saturated aqueous ammonium chloride solution was added thereto, and the mixture was extracted with ethyl acetate. The extract was washed with brine and dried over sodium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (hexane:ethyl acetate=83:17-80:20) to give 5-bromo-2-chlorophenyl-1-phenyl-4-pyrazolylmethanol (831 mg) as yellow oil. APCI-Mass m/Z 363/365 (M+H). (2) The above 5-bromo-2-chlorophenyl-1-phenyl-4-pyrazolylmethanol was treated in a manner similar to Reference Example 120-(2) to give the desired 5-bromo-2-chloro-1-(1-phenyl-4-pyrazolylmethyl)benzene as colorless powder. APCI-Mass m/Z 347/349 (M+H).

Workup

  1. additionadded dropwise
  2. additionadded dropwise
  3. stirringThe mixture was stirred at the same temperature for 30 minutes
  4. additionadded
  5. stirringthe mixture was stirred at 0° C. for further 30 minutes
  6. extractionthe mixture was extracted with ethyl acetate
  7. washThe extract was washed with brine
  8. dry with materialdried over sodium sulfate
  9. customThe solvent was evaporated under reduced pressure
  10. customthe residue was purified by silica gel column chromatography (hexane:ethyl acetate=83:17-80:20)

Sources & evidence

ORD record
ord-5d4b4e99305e499b9934c313385fbbf6
Source dataset
uspto-grants-2012_07
Patent number
US08222219B2

Reaction notes

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