Water → N-{1-[1-(3-chloro-5-trifluoromethyl-pyridin-2-yl)-cyclopropyl]-ethyl}-2,6-difluoro-benzamide

HRID 578857Notes

Reaction equation

HRID 578857 reaction equation
[Cl:1][C:2]1[C:3]([C:12]2([CH:15]([NH2:17])[CH3:16])[CH2:14][CH2:13]2)=[N:4][CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=1.C(N(CC)CC)C.[F:25][C:26]1[CH:34]=[CH:33][CH:32]=[C:31]([F:35])[C:27]=1[C:28](Cl)=[O:29].O>ClCCl>[Cl:1][C:2]1[C:3]([C:12]2([CH:15]([NH:17][C:28](=[O:29])[C:27]3[C:26]([F:25])=[CH:34][CH:33]=[CH:32][C:31]=3[F:35])[CH3:16])[CH2:14][CH2:13]2)=[N:4][CH:5]=[C:6]([C:8]([F:11])([F:9])[F:10])[CH:7]=1

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 874382,6-Difluorobenzoyl chlorideHCID 715591401-[1-(3-Chloro-5-trifluoromethyl-pyridin-2-yl)-cyclopropyl]-ethylamine

Product 1

HCID 71558840N-{1-[1-(3-chloro-5-trifluoromethyl-pyridin-2-yl)-cyclopropyl]-ethyl}-2,6-difluoro-benzamideYield 97.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

100 mg of 1-[1-(3-Chloro-5-trifluoromethyl-pyridin-2-yl)-cyclopropyl]-ethylamine (step 4) was dissolved in 4 ml of dichloromethane and cooled to 0° C. Then 76 mg of triethylamine was added, followed by dropwise addition of a solution of 67 mg of 2,6-difluorobenzoyl chloride in 1 ml of dichloromethane. The reaction mixture was stirred at ambient temperature for 2 hours. Then 20 ml of water were added and the mixture was extracted with 20 ml dichloromethane. The organic phase was dried over sodium sulfate, filtered and concentrated. Thus, 162 mg of crude material was obtained as a pale yellow oil. This residue was purified by chromatography on silica gel, with cyclohexane/ethyl acetate (85:15) as a eluent. Thus, 149 mg of N-{1-[1-(3-chloro-5-trifluoromethyl-pyridin-2-yl)-cyclopropyl]-ethyl}-2,6-difluoro-benzamide was obtained as a colourless sticky oil. 1H-NMR (CDCl3): 8.67 ppm (s, 1H), 7.93 ppm (s, 1H), 7.33 ppm (m, 1H), 6.93 ppm (t, 2H), 6.69 ppm (d, 1H, broad), 4.37 ppm (m, 1H), 1.25 ppm (d, 3H), 1.20 ppm (m, 4H).

Workup

  1. extractionthe mixture was extracted with 20 ml dichloromethane
  2. dry with materialThe organic phase was dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThus, 162 mg of crude material was obtained as a pale yellow oil
  6. customThis residue was purified by chromatography on silica gel, with cyclohexane/ethyl acetate (85:15) as a eluent

Sources & evidence

ORD record
ord-138fddc5425e4cd29f59e2a8766235a5
Source dataset
uspto-grants-2015_05
Patent number
US09040708B2

Reaction notes

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