Sodium hydride → N-(3-(trifluoromethyl)benzyl)-2-(2-nitro-5-(tetrahydro-2H-pyran-4-yloxy)phenyl)isonicotinamide

HRID 625286Notes

Reaction equation

HRID 625286 reaction equation
[O:1]1[CH2:6][CH2:5][CH:4]([OH:7])[CH2:3][CH2:2]1.[H-].[Na+].[F:10][C:11]([F:39])([F:38])[C:12]1[CH:13]=[C:14]([CH:35]=[CH:36][CH:37]=1)[CH2:15][NH:16][C:17](=[O:34])[C:18]1[CH:23]=[CH:22][N:21]=[C:20]([C:24]2[CH:29]=[C:28](F)[CH:27]=[CH:26][C:25]=2[N+:31]([O-:33])=[O:32])[CH:19]=1>CN(C)C=O.C(OCC)(=O)C>[F:38][C:11]([F:10])([F:39])[C:12]1[CH:13]=[C:14]([CH:35]=[CH:36][CH:37]=1)[CH2:15][NH:16][C:17](=[O:34])[C:18]1[CH:23]=[CH:22][N:21]=[C:20]([C:24]2[CH:29]=[C:28]([O:7][CH:4]3[CH2:5][CH2:6][O:1][CH2:2][CH2:3]3)[CH:27]=[CH:26][C:25]=2[N+:31]([O-:33])=[O:32])[CH:19]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 74956Tetrahydro-4H-pyran-4-olHCID 66586802N-(3-(trifluoromethyl)benzyl)-2-(5-fluoro-2-nitrophenyl)-isonicotinamide

Product 1

HCID 66586869N-(3-(trifluoromethyl)benzyl)-2-(2-nitro-5-(tetrahydro-2H-pyran-4-yloxy)phenyl)isonicotinamideYield 114%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Into a 50-mL round bottom flask, was placed a solution of tetrahydro-2H-pyran-4-ol (220 mg, 2.11 mmol, 3.00 equiv, 98%) in N,N-dimethylformamide (5 mL). This was followed by the addition of sodium hydride (86 mg, 3.58 mmol, 5.00 equiv), in portions at room temperature. The resulting solution was stirred for 10 min at room temperature. To this was added N-(3-(trifluoromethyl)benzyl)-2-(5-fluoro-2-nitrophenyl)isonicotinamide (300 mg, 0.70 mmol, 1.00 equiv, 98%). Then the resulting solution was stirred for an additional 2 h at 80° C. in an oil bath. The resulting solution was diluted with 200 mL of ethyl acetate, and washed with 2×30 mL of brine. The mixture was dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column and eluted with ethyl acetate/methanol (20/1). The product was obtained as 400 mg (97%) of a brown oil.

Workup

  1. customInto a 50-mL round bottom flask, was placed
  2. stirringThen the resulting solution was stirred for an additional 2 h at 80° C. in an oil bath
  3. washwashed with 2×30 mL of brine
  4. dry with materialThe mixture was dried over anhydrous sodium sulfate
  5. concentrationconcentrated under vacuum
  6. washeluted with ethyl acetate/methanol (20/1)

Sources & evidence

ORD record
ord-e5f337d26d9f47e9af77d258ca149dd7
Source dataset
uspto-grants-2016_04
Patent number
US09301951B2

Reaction notes

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