Triethylamine → 3-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid (2-hydroxy-1-methyl-ethyl)-amide

HRID 2189959Notes

Reaction equation

HRID 2189959 reaction equation
[F:1][CH:2]([F:12])[C:3]1[C:7]([C:8](Cl)=[O:9])=[CH:6][N:5]([CH3:11])[N:4]=1.[NH2:13][C@H:14]([CH2:16][OH:17])[CH3:15].C(N(CC)CC)C>ClCCl>[OH:17][CH2:16][CH:14]([NH:13][C:8]([C:7]1[C:3]([CH:2]([F:12])[F:1])=[N:4][N:5]([CH3:11])[CH:6]=1)=[O:9])[CH3:15]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 80307L-AlaninolHCID 153401103-(Difluoromethyl)-1-methyl-1 H-pyrazole-4-carbonyl chloride

Product 1

HCID 582314523-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid (2-hydroxy-1-methyl-ethyl)-amideYield 90%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

At 0° C., a solution of 38.9 g 3-difluoromethyl-1-methyl-1H-pyrazole-4-carbonyl chloride (0.2 mol) in 100 ml dichloromethane is added dropwise to a stirred solution of 15 g alaninol (0.2 mol) and 25 g triethylamine (0.25 mol) in 400 ml dichloromethane. The reaction mixture is stirred for 1 h at ambient temperature and then allowed to stand for 3 h at ambient temperature. After removal of the solvent the residue is purified by flash chromatography over silica gel 400 g (eluent: ethyl acetate/methanol 19:1). 42 g (90% of theory) of 3-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid (2-hydroxy-1-methyl-ethyl)-amide is obtained in form of a solid (mp. 81-87° C.).

Workup

  1. waitto stand for 3 h at ambient temperature
  2. customAfter removal of the solvent the residue
  3. customis purified by flash chromatography over silica gel 400 g (eluent: ethyl acetate/methanol 19:1)

Sources & evidence

ORD record
ord-e6a0c54364344c74b10e227b4d1865db
Source dataset
uspto-grants-2012_12
Patent number
US08324263B2

Reaction notes

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