3,5-Bis(trifluoromethyl)benzyl bromide → N-(3,5-bis-trifluoromethyl-benzyl)-6-chloro-N-methyl-4-o-tolyl-nicotinamide

HRID 1835304Notes

Reaction equation

HRID 1835304 reaction equation
[Cl:1][C:2]1[CH:11]=[C:10]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[CH3:18])[C:5]([C:6]([NH:8][CH3:9])=[O:7])=[CH:4][N:3]=1.C[Si](C)(C)[N-][Si](C)(C)C.[K+].[F:29][C:30]([F:44])([F:43])[C:31]1[CH:32]=[C:33]([CH:36]=[C:37]([C:39]([F:42])([F:41])[F:40])[CH:38]=1)[CH2:34]Br>O1CCCC1>[F:29][C:30]([F:44])([F:43])[C:31]1[CH:32]=[C:33]([CH:36]=[C:37]([C:39]([F:42])([F:41])[F:40])[CH:38]=1)[CH2:34][N:8]([CH3:9])[C:6](=[O:7])[C:5]1[C:10]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[CH3:18])=[CH:11][C:2]([Cl:1])=[N:3][CH:4]=1

Participants

5

Reactant 3

HCID 1225733,5-Bis(trifluoromethyl)benzyl bromideHCID 3251421Potassium bis(trimethylsilyl)amideHCID 121673126-chloro-N-methyl-4-o-tolyl-nicotinamide

Product 1

HCID 10277890N-(3,5-bis-trifluoromethyl-benzyl)-6-chloro-N-methyl-4-o-tolyl-nicotinamideYield 98.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 10.0 g (38.4 mmol) 6-chloro-N-methyl-4-o-tolyl-nicotinamide in 190 ml tetrahydrofuran 46 ml of a 1 M solution (46 mmol) of potassium hexamethyldisilazide in tetrahydrofuran were added at 0° C. After 30 min, 8.5 ml (46 mmol) 3,5-bis(trifluoromethyl)benzyl bromide were added dropwise to the resulting suspension. After completed addition the ice-water cooling bath was removed and the reaction mixture was allowed to warm to room temperature. After 2 h the reaction was quenched with water. The mixture was adjusted to pH 3 with 1 M aqueous hydrochloric acid solution and stirred for 10 min. Basification with 1 M aqueous sodium hydroxide solution to pH 8 was followed by concentration to remove tetrahydrofuran. The aqueous residue was extracted with four portions of dichloromethane. The combined organic extracts were dried with sodium sulfate and concentrated to give 21.4 g of crude product. Column chromatography afforded 18.4 g (98.5%) of the title compound as a white solid.

Workup

  1. customwas removed
  2. customAfter 2 h the reaction was quenched with water
  3. concentrationBasification with 1 M aqueous sodium hydroxide solution to pH 8 was followed by concentration
  4. customto remove tetrahydrofuran
  5. extractionThe aqueous residue was extracted with four portions of dichloromethane
  6. dry with materialThe combined organic extracts were dried with sodium sulfate
  7. concentrationconcentrated
  8. customto give 21.4 g of crude product

Sources & evidence

ORD record
ord-d43960f4e8a34b3e8dfbf248463fc0d1
Source dataset
uspto-grants-2004_08
Patent number
US06770637B2

Reaction notes

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