Water → 6-[3-(4-Chloro-phenyl)-isoxazol-4-ylmethoxy]-N-isopropyl-nicotinamide

HRID 1911687Notes

Reaction equation

HRID 1911687 reaction equation
C[Al](C)C.[CH:5]([NH2:8])([CH3:7])[CH3:6].CO[C:11](=[O:32])[C:12]1[CH:17]=[CH:16][C:15]([O:18][CH2:19][C:20]2[C:21]([C:25]3[CH:30]=[CH:29][C:28]([Cl:31])=[CH:27][CH:26]=3)=[N:22][O:23][CH:24]=2)=[N:14][CH:13]=1.O>O1CCOCC1>[Cl:31][C:28]1[CH:27]=[CH:26][C:25]([C:21]2[C:20]([CH2:19][O:18][C:15]3[CH:16]=[CH:17][C:12]([C:11]([NH:8][CH:5]([CH3:7])[CH3:6])=[O:32])=[CH:13][N:14]=3)=[CH:24][O:23][N:22]=2)=[CH:30][CH:29]=1

Participants

6

Reactant 4

HCID 962WaterHCID 6363IsopropylamineHCID 16682925TrimethylaluminumHCID 684427396-[3-(4-Chloro-phenyl)-isoxazol-4-ylmethoxy]-nicotinic acid methyl ester

Product 1

HCID 684437166-[3-(4-Chloro-phenyl)-isoxazol-4-ylmethoxy]-N-isopropyl-nicotinamideYield 56%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A solution of trimethylaluminium (2 M in toluene, 1.17 mL, 2.3 mmol) was added dropwise (exothermic) to a solution of isopropylamine (2.3 mmol) in dioxane (15 mL) and the resulting mixture was stirred at room temperature for 1.5 h. Then 6-[3-(4-chloro-phenyl)-isoxazol-4-ylmethoxy]-nicotinic acid methyl ester (200 mg, 0.58 mmol) was added. The resulting mixture was then heated at 85° C. for 2 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=2:1 to 1:1) afforded the title compound (120 mg, 56%) which was obtained as a white solid. MS: m/e=372.1 [M+H]+.

Workup

  1. temperatureThe resulting mixture was then heated at 85° C. for 2 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=2:1 to 1:1)

Sources & evidence

ORD record
ord-7f52f8c99a2040c985b6e678657bc40c
Source dataset
uspto-grants-2013_12
Patent number
US08604062B2

Reaction notes

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