Water → 6-[3-(4-Chloro-phenyl)-5-methyl-isoxazol-4-ylmethoxy]-N-(2,2,2-trifluoro-ethyl)-nicotinamide

HRID 1897136Notes

Reaction equation

HRID 1897136 reaction equation
C[Al](C)C.[F:5][C:6]([F:10])([F:9])[CH2:7][NH2:8].C[O:12][C:13](=O)[C:14]1[CH:19]=[CH:18][C:17]([O:20][CH2:21][C:22]2[C:23]([C:28]3[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][CH:29]=3)=[N:24][O:25][C:26]=2[CH3:27])=[N:16][CH:15]=1.O>O1CCOCC1>[Cl:34][C:31]1[CH:30]=[CH:29][C:28]([C:23]2[C:22]([CH2:21][O:20][C:17]3[CH:18]=[CH:19][C:14]([C:13]([NH:8][CH2:7][C:6]([F:10])([F:9])[F:5])=[O:12])=[CH:15][N:16]=3)=[C:26]([CH3:27])[O:25][N:24]=2)=[CH:33][CH:32]=1

Participants

6

Reactant 4

HCID 962WaterHCID 9773Ethanamine, 2,2,2-trifluoro-HCID 16682925TrimethylaluminumHCID 426293306-[3-(4-Chloro-phenyl)-5-methyl-isoxazol-4-ylmethoxy]-nicotinic acid methyl ester

Product 1

HCID 426293316-[3-(4-Chloro-phenyl)-5-methyl-isoxazol-4-ylmethoxy]-N-(2,2,2-trifluoro-ethyl)-nicotinamideYield 77.5%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

A solution of trimethylaluminium (2 M in toluene, 401 μL, 0.8 mmol) was added dropwise (exothermic) to a solution of 2,2,2-trifluoroethylamine (79 mg, 63 μL, 0.8 mmol) in dioxane (5 mL) and the resulting mixture was stirred at room temperature for 1 h. Then a solution of 6-[3-(4-chloro-phenyl)-5-methyl-isoxazol-4-ylmethoxy]-nicotinic acid methyl ester (72 mg, 0.2 mmol) in dioxane (2.5 mL) was added. The resulting mixture was then heated at 85-95° C. for 1 h and then cooled to room temperature and then poured into water and extracted with ethyl acetate which was then washed with brine, dried over sodium sulfate and evaporated. Purification by chromatography (SiO2, heptane:ethyl acetate=100:0 to 1:1) afforded the title compound (66 mg, 77%) which was obtained as a white solid. MS: m/e=426.0 [M+H]+.

Workup

  1. temperatureThe resulting mixture was then heated at 85-95° C. for 1 h
  2. temperaturecooled to room temperature
  3. extractionextracted with ethyl acetate which
  4. washwas then washed with brine
  5. dry with materialdried over sodium sulfate
  6. customevaporated
  7. customPurification by chromatography (SiO2, heptane:ethyl acetate=100:0 to 1:1)

Sources & evidence

ORD record
ord-39bd348e1d504466bc5bb75df2b39cbc
Source dataset
uspto-grants-2013_08
Patent number
US08518974B2

Reaction notes

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