Pyridine → (1S,6R,9aR)-6-(3,4-difluorophenyl)-1-methyltetrahydro-[1,4]oxazino[3,4-c][1,4]oxazine-3,4-dione
Reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C@H:9]2[NH:14][C@@H:13]([CH:15]([OH:17])[CH3:16])[CH2:12][O:11][CH2:10]2)[CH:5]=[CH:6][C:7]=1[F:8].N1C=CC=CC=1.[C:24](Cl)(=[O:28])[C:25](Cl)=[O:26]>ClCCl.O>[F:1][C:2]1[CH:3]=[C:4]([C@@H:9]2[CH2:10][O:11][CH2:12][C@@H:13]3[C@H:15]([CH3:16])[O:17][C:24](=[O:28])[C:25](=[O:26])[N:14]23)[CH:5]=[CH:6][C:7]=1[F:8]Participants
6
Reactant 3
Product 1
Reagents, catalysts & solvents 2
Procedure
To a solution consisting of 1-[(3R,5R)-5-(3,4-difluorophenyl)morpholine-3-yl]ethanol (424 mg) and pyridine (2 mL) in dichloromethane (8 mL) was dropwise added oxalyl chloride (417 μL) while cooling with ice. The resultant solution was stirred at the same temperature for 30 minutes. The reaction solution was diluted with water, and the organic layer was partitioned. The organic layer was then dried over magnesium sulfate. Solvent was removed by distillation under reduced pressure, and the resulting residue was purified by silica gel column chromatography (heptane/ethyl acetate 9/1→1/4), to thereby obtain the titled compound (353 mg). The physical properties of the compound were as follows.
Workup
- temperaturewhile cooling with ice
- customthe organic layer was partitioned
- dry with materialThe organic layer was then dried over magnesium sulfate
- customSolvent was removed by distillation under reduced pressure
- customthe resulting residue was purified by silica gel column chromatography (heptane/ethyl acetate 9/1→1/4)
Sources & evidence
- ORD record
- ord-257e7e727ab7428bbfc3c4d84c9c9624
- Source dataset
- uspto-grants-2010_06
- Patent number
- US07737141B2
Reaction notes
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