2,6-Dimethylmorpholine → rac-(2S,6R)-2,6-Dimethyl-4-{4-[5-(5-methyl-3-phenyl-isoxazol-4-yl)-[1,3,4]oxadiazol-2-yl]-phenyl}-morpholine

HRID 2421130Notes

Reaction equation

HRID 2421130 reaction equation
F[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][C:10]([C:13]3[C:14]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)=[N:15][O:16][C:17]=3[CH3:18])=[N:11][N:12]=2)=[C:4](OC)[CH:3]=1.[CH3:27][CH:28]1[O:33][CH:32]([CH3:34])[CH2:31][NH:30][CH2:29]1>CS(C)=O>[CH3:34][CH:32]1[O:33][CH:28]([CH3:27])[CH2:29][N:30]([C:2]2[CH:3]=[CH:4][C:5]([C:8]3[O:9][C:10]([C:13]4[C:14]([C:19]5[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=5)=[N:15][O:16][C:17]=4[CH3:18])=[N:11][N:12]=3)=[CH:6][CH:7]=2)[CH2:31]1

Participants

4

Reactant 2

HCID 1108622,6-Dimethylmorpholine2×HCID 167226452-(4-Fluoro-2-methoxy-phenyl)-5-(5-methyl-3-phenyl-isoxazol-4-yl)-[1,3,4]oxadiazole

Product 1

HCID 67215637rac-(2S,6R)-2,6-Dimethyl-4-{4-[5-(5-methyl-3-phenyl-isoxazol-4-yl)-[1,3,4]oxadiazol-2-yl]-phenyl}-morpholineYield 24%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
200 °C

Procedure

A suspension of 2-(4-fluoro-2-methoxy-phenyl)-5-(5-methyl-3-phenyl-isoxazol-4-yl)-[1,3,4]oxadiazole (200 mg, 0.62 mmol) in 2,6-dimethylmorpholine (2.00 mL, 16.0 mmol) was heated for 30 min at 200° C. (microwave) followed by stirring under gently reflux for 18 h at 160° C. After addition of DMSO (2 mL) and 2,6-dimethylmorpholine (0.50 mL, 4.00 mmol) the solution was stirred for another 24 h at 160° C. After cooling to ambient temperature the reaction mixture was extracted with water (20 mL) and ethyl acetate (20 mL). The aqueous layer was extracted with ethyl acetate (20 mL) and the combined organic layers were washed with brine (20 mL) and aqueous sodium carbonate (saturated, 20 mL). Drying over sodium sulfate, concentration and purification by chromatography (SiO2, heptane:ethyl acetate:dichloromethane=70:10:20 to 40:40:20) afforded the title compound (61 mg, 24%) as a white solid. MS: m/e=417.3 [M+H]+.

Workup

  1. temperatureunder gently reflux for 18 h at 160° C
  2. stirringwas stirred for another 24 h at 160° C
  3. temperatureAfter cooling to ambient temperature the reaction mixture
  4. extractionwas extracted with water (20 mL) and ethyl acetate (20 mL)
  5. extractionThe aqueous layer was extracted with ethyl acetate (20 mL)
  6. washthe combined organic layers were washed with brine (20 mL) and aqueous sodium carbonate (saturated, 20 mL)
  7. dry with materialDrying over sodium sulfate, concentration and purification by chromatography (SiO2, heptane:ethyl acetate:dichloromethane=70:10:20 to 40:40:20)

Sources & evidence

ORD record
ord-b827cb047bd94e9cb90445f305c1b3d0
Source dataset
uspto-grants-2011_06
Patent number
US07956074B2

Reaction notes

Loading…