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 1677093Notes

Reaction equation

HRID 1677093 reaction equation
[C:1](Cl)(=[O:5])[C:2](Cl)=[O:3].C(Cl)(Cl)Cl.N1C=CC=CC=1.[F:17][C:18]1[CH:19]=[C:20]([C@H:26]2[NH:31][C@@H:30]([C:32]([OH:35])([CH3:34])[CH3:33])[CH2:29][O:28][CH2:27]2)[CH:21]=[C:22]([F:25])[C:23]=1[F:24]>O>[CH3:34][C:32]1([CH3:33])[C@H:30]2[CH2:29][O:28][CH2:27][C@@H:26]([C:20]3[CH:19]=[C:18]([F:17])[C:23]([F:24])=[C:22]([F:25])[CH:21]=3)[N:31]2[C:2](=[O:3])[C:1](=[O:5])[O:35]1

Participants

6

Reactant 4

HCID 1049PyridineHCID 6212ChloroformHCID 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 1

HCID 962WaterSolvent

Procedure

Under ice-cooling, oxalyl chloride (205 μL) was added dropwise into a chloroform (10 mL) solution of pyridine (2 mL) and 2-[(3R,5R)-5-(3,4,5-trifluorophenyl)morpholin-3-yl]propane-2-ol (330 mg). The reaction solution was stirred for 1 hour at the same temperature, and the resultant was stirred a further 2 hours at room temperature. Water was added to the reaction solution, and the organic layer was partitioned. The organic layer was washed with brine and dried over anhydrous magnesium sulfate, and the solvent was removed under a vacuum. The residue was purified by silica gel column chromatography (heptane/ethyl acetate), and the title compound (260 mg) was obtained. The physical property values are as follows.

Workup

  1. temperatureUnder ice-cooling
  2. stirringthe resultant was stirred a further 2 hours at room temperature
  3. customthe organic layer was partitioned
  4. washThe organic layer was washed with brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customthe solvent was removed under a vacuum
  7. customThe residue was purified by silica gel column chromatography (heptane/ethyl acetate)

Sources & evidence

ORD record
ord-69c55e8f3c2f4799a82e83e290a8ac07
Source dataset
uspto-grants-2011_08
Patent number
US08008293B2

Reaction notes

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