Water → (1,1-Dioxo-1lambda6-thiomorpholin-4-yl)-{6-[3-(4-fluoro-phenyl)-5-trifluoromethyl-isoxazol-4-ylmethoxy]-pyridin-3-yl}-methanone

HRID 83270Notes

Reaction equation

HRID 83270 reaction equation
C[Al](C)C.[NH:5]1[CH2:10][CH2:9][S:8](=[O:12])(=[O:11])[CH2:7][CH2:6]1.C[O:14][C:15](=O)[C:16]1[CH:21]=[CH:20][C:19]([O:22][CH2:23][C:24]2[C:25]([C:33]3[CH:38]=[CH:37][C:36]([F:39])=[CH:35][CH:34]=3)=[N:26][O:27][C:28]=2[C:29]([F:32])([F:31])[F:30])=[N:18][CH:17]=1.O>O1CCOCC1>[O:11]=[S:8]1(=[O:12])[CH2:9][CH2:10][N:5]([C:15]([C:16]2[CH:17]=[N:18][C:19]([O:22][CH2:23][C:24]3[C:25]([C:33]4[CH:34]=[CH:35][C:36]([F:39])=[CH:37][CH:38]=4)=[N:26][O:27][C:28]=3[C:29]([F:30])([F:32])[F:31])=[CH:20][CH:21]=2)=[O:14])[CH2:6][CH2:7]1

Participants

6

Reactant 4

HCID 962WaterHCID 6484228Thiomorpholine 1,1-dioxideHCID 16682925TrimethylaluminumHCID 684447756-[3-(4-Fluoro-phenyl)-5-trifluoromethyl-isoxazol-4-ylmethoxy]-nicotinic acid methyl ester

Product 1

HCID 68935506(1,1-Dioxo-1lambda6-thiomorpholin-4-yl)-{6-[3-(4-fluoro-phenyl)-5-trifluoromethyl-isoxazol-4-ylmethoxy]-pyridin-3-yl}-methanoneYield 25.6%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

A solution of trimethylaluminium (2 M in toluene, 504 μL, 1.0 mmol) was added dropwise (exothermic) to a solution of thiomorpholine-S,S-dioxide (136 mg, 1.0 mmol) in dioxane (7 mL) and the resulting mixture was stirred at room temperature for 1 h. Then a solution of 6-[3-(4-fluoro-phenyl)-5-trifluoromethyl-isoxazol-4-ylmethoxy]-nicotinic acid methyl ester (100 mg, 0.25 mmol) in dioxane (4 mL) was added. The resulting mixture was then heated at 85-95° C. for 4 days 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 (32 mg, 25%) which was obtained as an off white solid. MS: m/e=500.0 [M+H]+.

Workup

  1. temperatureThe resulting mixture was then heated at 85-95° C. for 4 days
  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-2311af665beb4880a462f2820fd2c245
Source dataset
uspto-grants-2014_09
Patent number
US08846719B2

Reaction notes

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