Sodium hydride → 2-(5-cyclobutoxy-2-nitrophenyl)-N-(3-(trifluoromethyl)benzyl)isonicotinamide

HRID 625321Notes

Reaction equation

HRID 625321 reaction equation
[CH:1]1([OH:5])[CH2:4][CH2:3][CH2:2]1.[H-].[Na+].[F:8][C:9]([F:37])([F:36])[C:10]1[CH:11]=[C:12]([CH:33]=[CH:34][CH:35]=1)[CH2:13][NH:14][C:15](=[O:32])[C:16]1[CH:21]=[CH:20][N:19]=[C:18]([C:22]2[CH:27]=[C:26](F)[CH:25]=[CH:24][C:23]=2[N+:29]([O-:31])=[O:30])[CH:17]=1>CN(C=O)C>[CH:1]1([O:5][C:26]2[CH:25]=[CH:24][C:23]([N+:29]([O-:31])=[O:30])=[C:22]([C:18]3[CH:17]=[C:16]([CH:21]=[CH:20][N:19]=3)[C:15]([NH:14][CH2:13][C:12]3[CH:33]=[CH:34][CH:35]=[C:10]([C:9]([F:8])([F:36])[F:37])[CH:11]=3)=[O:32])[CH:27]=2)[CH2:4][CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 76218CyclobutanolHCID 66586802N-(3-(trifluoromethyl)benzyl)-2-(5-fluoro-2-nitrophenyl)-isonicotinamide

Product 1

HCID 665876992-(5-cyclobutoxy-2-nitrophenyl)-N-(3-(trifluoromethyl)benzyl)isonicotinamideYield 73.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A 25° C. solution of 26 mg of cyclobutanol in 0.5 mL of DMF was treated with 10 mg of 60% NaH in oil. After stirring for 15 minutes, 75 mg of 2-(5-fluoro-2-nitrophenyl)-N-(3-(trifluoromethyl)benzyl)isonicotinamide 14d was added. The mixture was stirred overnight and then it was quenched with water. It was diluted with ethyl acetate, and the resulting solution was washed with water, then with brine. The solution was dried (Na2SO4) and the solvent was removed at reduced pressure. The residue was purified by chromatography on silica gel to give 62 mg of a syrup.

Workup

  1. stirringThe mixture was stirred overnight
  2. customit was quenched with water
  3. additionIt was diluted with ethyl acetate
  4. washthe resulting solution was washed with water
  5. dry with materialThe solution was dried (Na2SO4)
  6. customthe solvent was removed at reduced pressure
  7. customThe residue was purified by chromatography on silica gel

Sources & evidence

ORD record
ord-b8022d34fd9641cd9feb6a066dbb2f2f
Source dataset
uspto-grants-2016_04
Patent number
US09301951B2

Reaction notes

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