Water → N-Isopropyl-6-(3-phenyl-5-trifluoromethyl-isoxazol-4-ylmethoxy)-nicotinamide

HRID 1897154Notes

Reaction equation

HRID 1897154 reaction equation
C[Al](C)C.[CH:5]([NH2:8])([CH3:7])[CH3:6].C[O:10][C:11](=O)[C:12]1[CH:17]=[CH:16][C:15]([O:18][CH2:19][C:20]2[C:21]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)=[N:22][O:23][C:24]=2[C:25]([F:28])([F:27])[F:26])=[N:14][CH:13]=1.O>O1CCOCC1>[CH:5]([NH:8][C:11](=[O:10])[C:12]1[CH:17]=[CH:16][C:15]([O:18][CH2:19][C:20]2[C:21]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)=[N:22][O:23][C:24]=2[C:25]([F:28])([F:27])[F:26])=[N:14][CH:13]=1)([CH3:7])[CH3:6]

Participants

6

Reactant 4

HCID 962WaterHCID 6363IsopropylamineHCID 16682925TrimethylaluminumHCID 684432696-(3-Phenyl-5-trifluoromethyl-isoxazol-4-ylmethoxy)-nicotinic acid methyl ester

Product 1

HCID 68444357N-Isopropyl-6-(3-phenyl-5-trifluoromethyl-isoxazol-4-ylmethoxy)-nicotinamideYield 96.8%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

A solution of trimethylaluminium (2 M in toluene, 529 μL, 1.1 mmol) was added dropwise (exothermic) to a solution of isopropylamine (63 mg, 91 μL, 1.1 mmol) in dioxane (7 mL) and the resulting mixture was stirred at room temperature for 1 h. Then a solution of 6-(3-phenyl-5-trifluoromethyl-isoxazol-4-ylmethoxy)-nicotinic acid methyl ester (100 mg, 0.26 mmol) in dioxane (4 mL) was added. The resulting mixture was then heated at 85-95° C. for 5 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 (102 mg, 95%) which was obtained as a white solid. MS: m/e=406.4 [M+H]+.

Workup

  1. temperatureThe resulting mixture was then heated at 85-95° C. for 5 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-baf69843947743b2be786211bcdd5bb6
Source dataset
uspto-grants-2013_08
Patent number
US08518974B2

Reaction notes

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