Dimethylformamide → N-(5-tert-butyl-2-hydroxyphenyl)-3-fluoroisonicotinamide

HRID 1913738Notes

Reaction equation

HRID 1913738 reaction equation
[F:1][C:2]1[CH:10]=[N:9][CH:8]=[CH:7][C:3]=1[C:4](Cl)=[O:5].CN(C=O)C.[NH2:16][C:17]1[CH:22]=[C:21]([C:23]([CH3:26])([CH3:25])[CH3:24])[CH:20]=[CH:19][C:18]=1[OH:27].C(N(CC)CC)C>O>[C:23]([C:21]1[CH:20]=[CH:19][C:18]([OH:27])=[C:17]([NH:16][C:4](=[O:5])[C:3]2[CH:7]=[CH:8][N:9]=[CH:10][C:2]=2[F:1])[CH:22]=1)([CH3:26])([CH3:24])[CH3:25]

Participants

6

Reactant 4

HCID 6228Dimethylformamide2×HCID 8471TriethylamineHCID 709822-Amino-4-tert-butylphenolHCID 232877573-Fluoroisonicotinoyl chloride

Product 1

HCID 66880592N-(5-tert-butyl-2-hydroxyphenyl)-3-fluoroisonicotinamide

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of 1.5 g of 3-fluoroisonicotinic acid, 5 ml of thionyl chloride and 50 mg of DMF was heated to reflux for two hours. The reaction mixture was cooled to room temperature, and then the reaction mixture was concentrated under reduced pressure to give 3-fluoroisonicotinic acid chloride. A mixture of the resultant 3-fluoroisonicotinic acid chloride and 5 ml of DMF was added dropwise to a mixture of 1.76 g of 2-amino-4-tert-butylphenol, 2.18 g of triethylamine and 10 ml of DMF while ice-cooling. The reaction mixture was stirred at room temperature for 1.5 hours and at 50° C. for 30 minutes. The reaction mixture was cooled to room temperature, and then water was added. Precipitated crystals were collected by filtration. The resultant crystals were dissolved in ethyl acetate, washed with water and a saturated sodium chloride solution, dried over anhydrous magnesium sulfate, concentrated under reduced pressure to give 2.41 g of N-(5-tert-butyl-2-hydroxyphenyl)-3-fluoroisonicotinamide.

Workup

  1. temperaturecooling
  2. temperatureThe reaction mixture was cooled to room temperature
  3. customPrecipitated crystals
  4. filtrationwere collected by filtration
  5. dissolutionThe resultant crystals were dissolved in ethyl acetate
  6. washwashed with water
  7. dry with materiala saturated sodium chloride solution, dried over anhydrous magnesium sulfate
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-04f4c510dec845f7bfab6c01280d1f15
Source dataset
uspto-grants-2013_12
Patent number
US08609705B2

Reaction notes

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