Triethylamine → 3-(Difluoromethyl)-N-methoxy-1-methyl-N-(1-methyl-2-(2,4,6-trichlorophenyl)ethyl)-1H-pyrazole-4-carboxamide

HRID 2170303Notes

Reaction equation

HRID 2170303 reaction equation
[CH3:1][O:2][NH:3][CH:4]([CH3:15])[CH2:5][C:6]1[C:11]([Cl:12])=[CH:10][C:9]([Cl:13])=[CH:8][C:7]=1[Cl:14].C(N(CC)CC)C.[F:23][CH:24]([F:34])[C:25]1[C:29]([C:30](Cl)=[O:31])=[CH:28][N:27]([CH3:33])[N:26]=1>ClCCl>[CH3:1][O:2][N:3]([CH:4]([CH3:15])[CH2:5][C:6]1[C:7]([Cl:14])=[CH:8][C:9]([Cl:13])=[CH:10][C:11]=1[Cl:12])[C:30]([C:29]1[C:25]([CH:24]([F:34])[F:23])=[N:26][N:27]([CH3:33])[CH:28]=1)=[O:31]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 153401103-(Difluoromethyl)-1-methyl-1 H-pyrazole-4-carbonyl chlorideHCID 58443683N-methoxy-1-(2,4,6-trichlorophenyl)propan-2-amine

Product 1

HCID 569334113-(Difluoromethyl)-N-methoxy-1-methyl-N-(1-methyl-2-(2,4,6-trichlorophenyl)ethyl)-1H-pyrazole-4-carboxamideYield 41%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of O-methyl-N-[1-methyl-2-(2,4,6-trichloro-phenyl)-ethyl]-hydroxylamine (12.3 g, 0.046 mol) prepared as described in example P5a, in dichloromethane (120 ml) was added triethylamine (7.7 ml, 0.055 mol) followed by dropwise addition of a solution of 3-difluoromethyl-1-methyl-1H-pyrazole-4-carbonyl chloride (9.1 g, 0.046 mol) in dichloromethane (10 ml) at 0° C. After complete addition of acid chloride the mixture was stirred 5 hours at ambient temperature. When the TLC confirmed completion of the reaction, the reaction mass was washed with 1N HCl (100 ml), followed by 1N NaOH (100 ml), then with water (2×100 ml) and finally with brine solution (50 ml) before drying over sodium sulfate and evaporation of the solvent. The resulting crude mass 20.5 g of a sticky dark brown oil was purified by column chromatography using 60-120μ mesh silica gel and product collected at 40% ethyl acetate in hexane as eluent to give 3-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid methoxy-[1-methyl-2-(2,4,6-trichloro-phenyl)-ethyl]-amide (7.9 g, 41%) as off white solid. m.p: 110-112° C. 1H NMR (400 MHz, CDCl3): δ1.38-1.39 (d, 3H), 3.20-3.26 (dd, 1H), 3.32-3.37 (dd, 1H), 3.70 (s, 3H), 3.97 (s, 3H), 4.88-4.93 (m, 1H), 7.02-7.29 (t, 1H), 7.27 (s, 2H), 7.81 (s, 1H) MS [M+H]+ 426/428/430

Workup

  1. customcompletion of the reaction
  2. washthe reaction mass was washed with 1N HCl (100 ml)
  3. dry with materialwith water (2×100 ml) and finally with brine solution (50 ml) before drying over sodium sulfate and evaporation of the solvent
  4. customThe resulting crude mass 20.5 g of a sticky dark brown oil was purified by column chromatography
  5. customcollected at 40% ethyl acetate in hexane as eluent

Sources & evidence

ORD record
ord-15fb87bae654401fb02916b41dc0e73a
Source dataset
uspto-grants-2015_06
Patent number
US09051272B2

Reaction notes

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