Ethanamine, 2,2,2-trifluoro- → 6-(5-Methyl-3-phenyl-isoxazol-4-ylmethoxy)-N-(2,2,2-trifluoro-ethyl)-nicotinamide

HRID 1520983Notes

Reaction equation

HRID 1520983 reaction equation
[CH3:1][C:2]1[O:6][N:5]=[C:4]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[C:3]=1[CH2:13][O:14][C:15]1[CH:23]=[CH:22][C:18]([C:19]([OH:21])=O)=[CH:17][N:16]=1.F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.[F:55][C:56]([F:60])([F:59])[CH2:57][NH2:58]>CN(C=O)C>[CH3:1][C:2]1[O:6][N:5]=[C:4]([C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=2)[C:3]=1[CH2:13][O:14][C:15]1[CH:23]=[CH:22][C:18]([C:19]([NH:58][CH2:57][C:56]([F:60])([F:59])[F:55])=[O:21])=[CH:17][N:16]=1

Participants

6

Reactant 4

HCID 9773Ethanamine, 2,2,2-trifluoro-HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 665992136-(5-Methyl-3-phenyl-isoxazol-4-ylmethoxy)-nicotinic acid

Product 1

HCID 575199256-(5-Methyl-3-phenyl-isoxazol-4-ylmethoxy)-N-(2,2,2-trifluoro-ethyl)-nicotinamideYield 85%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 6-(5-methyl-3-phenyl-isoxazol-4-ylmethoxy)-nicotinic acid (200 mg, 0.64 mmol) in DMF (2 mL) were added 2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (228 mg, 0.71 mmol), N,N-diisopropyl ethyl amine (552 μL, 3.22 mmol) and 2,2,2-trifluoroethylamine 77 μL, 0.77 mmol). The resulting reaction mixture was stirred for 12 h at ambient temperature. After dilution with ethyl acetate (20 mL) it was washed with water (20 mL) and aqueous sodium carbonate (saturated, 40 mL). The organic layer was dried over sodium sulfate and concentrated. Purification by chromatography (SiO2, heptane:ethyl acetate=80:20 to 20:80) afforded the title compound (213 mg, 84%) as a white solid. MS: m/e=392.2 [M+H]+.

Workup

  1. customThe resulting reaction mixture
  2. washAfter dilution with ethyl acetate (20 mL) it was washed with water (20 mL) and aqueous sodium carbonate (saturated, 40 mL)
  3. dry with materialThe organic layer was dried over sodium sulfate
  4. concentrationconcentrated
  5. customPurification by chromatography (SiO2, heptane:ethyl acetate=80:20 to 20:80)

Sources & evidence

ORD record
ord-6471614b539842889c2feaa398d4ac7d
Source dataset
uspto-grants-2015_07
Patent number
US09073908B2

Reaction notes

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