Pyridine → (1S,6R,9aR)-6-(4-chlorophenyl)-1-methyltetrahydro-[1,4]oxazino[3,4-c][1,4]oxazine-3,4-dione

HRID 16380Notes

Reaction equation

HRID 16380 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]2[NH:13][C@@H:12]([C@@H:14]([OH:16])[CH3:15])[CH2:11][O:10][CH2:9]2)=[CH:4][CH:3]=1.N1C=CC=CC=1.[C:23](Cl)(=[O:27])[C:24](Cl)=[O:25]>ClCCl.O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C@@H:8]2[CH2:9][O:10][CH2:11][C@@H:12]3[C@H:14]([CH3:15])[O:16][C:23](=[O:27])[C:24](=[O:25])[N:13]23)=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 1049PyridineHCID 65578Oxalyl chlorideHCID 68716014(S)-1-[(3R,5R)-5-(4-chlorophenyl)morpholine-3-yl]ethanol

Product 1

HCID 67374837(1S,6R,9aR)-6-(4-chlorophenyl)-1-methyltetrahydro-[1,4]oxazino[3,4-c][1,4]oxazine-3,4-dione

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution consisting of (S)-1-[(3R,5R)-5-(4-chlorophenyl)morpholine-3-yl]ethanol (833 g) and pyridine (4 mL) in dichloromethane (15 mL) was dropwise added oxalyl chloride (833 μL) while cooling with ice. The resultant solution was stirred at the same temperature for 30 minutes, and then at room temperature for 1 hour. The reaction solution was diluted with water, and the organic layer was partitioned. The organic layer was then dried over anhydrous magnesium sulfate. Solvent was removed by distillation under reduced pressure, and the resulting residue was purified by silica gel column chromatography (heptane/ethyl acetate→ethyl acetate), to thereby obtain the titled compound (686 mg). The physical properties of the compound were as follows. ESI-MS; m/z 296 [M++H]. 1H-NMR (CDCl3) δ (ppm): 1.51 (d, J=6.4 Hz, 3H), 3.52 (dd, J=12.0, 12.0 Hz, 1H), 3.78 (dd, J=12.4, 8.0 Hz, 1H), 4.02 (dd, J=11.6, 4.4 Hz, 1H), 4.18 (dd, J=12.4, 4.8 Hz, 1H), 4.51 (ddd, J=11.2, 4.0, 4.0 Hz, 1H), 4.61-4.67 (m, 1H), 4.89 (dd, J=8.0, 4.8 Hz, 1H), 7.32 (s, 4H).

Workup

  1. temperaturewhile cooling with ice
  2. customthe organic layer was partitioned
  3. dry with materialThe organic layer was then dried over anhydrous magnesium sulfate
  4. customSolvent was removed by distillation under reduced pressure
  5. customthe resulting residue was purified by silica gel column chromatography (heptane/ethyl acetate→ethyl acetate)

Sources & evidence

ORD record
ord-a286814f90cb43f9a9f83fa6915012ad
Source dataset
uspto-grants-2010_06
Patent number
US07737141B2

Reaction notes

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