Water → {6-[3-(3-Fluoro-phenyl)-5-methyl-isoxazol-4-ylmethoxy]-pyridin-3-yl}-thiomorpholin-4-yl-methanone

HRID 1897109Notes

Reaction equation

HRID 1897109 reaction equation
C[Al](C)C.[NH:5]1[CH2:10][CH2:9][S:8][CH2:7][CH2:6]1.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][CH:31]=[C:30]([F:34])[CH:29]=3)=[N:24][O:25][C:26]=2[CH3:27])=[N:16][CH:15]=1.O>O1CCOCC1>[F:34][C:30]1[CH:29]=[C:28]([C:23]2[C:22]([CH2:21][O:20][C:17]3[N:16]=[CH:15][C:14]([C:13]([N:5]4[CH2:10][CH2:9][S:8][CH2:7][CH2:6]4)=[O:12])=[CH:19][CH:18]=3)=[C:26]([CH3:27])[O:25][N:24]=2)[CH:33]=[CH:32][CH:31]=1

Participants

6

Reactant 4

HCID 962WaterHCID 67164ThiomorpholineHCID 16682925TrimethylaluminumHCID 684418946-[3-(3-Fluoro-phenyl)-5-methyl-isoxazol-4-ylmethoxy]-nicotinic acid methyl ester

Product 1

HCID 68936363{6-[3-(3-Fluoro-phenyl)-5-methyl-isoxazol-4-ylmethoxy]-pyridin-3-yl}-thiomorpholin-4-yl-methanoneYield 100%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

A solution of trimethylaluminium (2 M in toluene, 600 μL, 1.2 mmol) was added dropwise (exothermic) to a solution of thiomorpholine (124 mg, 120 μL, 1.2 mmol) in dioxane (7.5 mL) and the resulting mixture was stirred at room temperature for 1 h. Then a solution of 6-[3-(3-fluoro-phenyl)-5-methyl-isoxazol-4-ylmethoxy]-nicotinic acid methyl ester (103 mg, 0.3 mmol) in dioxane (4 mL) was added. The resulting mixture was then heated at 85-95° C. for 4 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 1:3) afforded the title compound (124 mg, 100%) which was obtained as a light yellow gum. MS: m/e=414.4 [M+H]+.

Workup

  1. temperatureThe resulting mixture was then heated at 85-95° C. for 4 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 1:3)

Sources & evidence

ORD record
ord-a64ac01de42a4597964b023bb2cc7c69
Source dataset
uspto-grants-2013_08
Patent number
US08518974B2

Reaction notes

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