Pyridine → (6R,9aR)-1,1-dimethyl-6-(3,4,5-trifluorophenyl)tetrahydro [1,4]oxazino[3,4-c][1,4]oxazine-3,4-dione

HRID 16392Notes

Reaction equation

HRID 16392 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C@H:10]2[NH:15][C@@H:14]([C:16]([OH:19])([CH3:18])[CH3:17])[CH2:13][O:12][CH2:11]2)[CH:5]=[C:6]([F:9])[C:7]=1[F:8].N1C=CC=CC=1.[C:26](Cl)(=[O:30])[C:27](Cl)=[O:28]>C(Cl)(Cl)Cl.O>[CH3:18][C:16]1([CH3:17])[C@H:14]2[CH2:13][O:12][CH2:11][C@@H:10]([C:4]3[CH:3]=[C:2]([F:1])[C:7]([F:8])=[C:6]([F:9])[CH:5]=3)[N:15]2[C:27](=[O:28])[C:26](=[O:30])[O:19]1

Participants

6

Reactant 3

HCID 1049PyridineHCID 65578Oxalyl chlorideHCID 673733842-[(3R,5R)-5-(3,4,5-trifluorophenyl)morpholine-3-yl]propane-2-ol

Product 1

HCID 67373385(6R,9aR)-1,1-dimethyl-6-(3,4,5-trifluorophenyl)tetrahydro [1,4]oxazino[3,4-c][1,4]oxazine-3,4-dione

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6212ChloroformSolvent

Procedure

To a solution of 2-[(3R,5R)-5-(3,4,5-trifluorophenyl)morpholine-3-yl]propane-2-ol (330 mg) and pyridine (2 mL) in chloroform (10 mL) was dropwise added oxalyl chloride (205 μL) while cooling with ice. The resultant solution was stirred at the same temperature for 1 hour, and then stirred for another 2 hours at room temperature. The resultant solution was diluted with water, and the organic layer was partitioned. The organic layer was washed with brine and then dried over anhydrous magnesium sulfate. Solvent was removed by distillation under reduced pressure. The resultant residue was purified by silica gel column chromatography (heptane/ethyl acetate), to thereby obtain the titled compound (260 mg). The physical properties of this crude product were as follows.

Workup

  1. temperaturewhile cooling with ice
  2. customthe organic layer was partitioned
  3. washThe organic layer was washed with brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customSolvent was removed by distillation under reduced pressure
  6. customThe resultant residue was purified by silica gel column chromatography (heptane/ethyl acetate)

Sources & evidence

ORD record
ord-4fd20f8db3314aaea9b31d5fcab683e4
Source dataset
uspto-grants-2010_06
Patent number
US07737141B2

Reaction notes

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