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

HRID 1677057Notes

Reaction equation

HRID 1677057 reaction equation
[C:1](Cl)(=[O:5])[C:2](Cl)=[O:3].ClCCl.[F:10][C:11]1[CH:12]=[C:13]([C@H:18]2[NH:23][C@@H:22]([CH:24]([OH:26])[CH3:25])[CH2:21][O:20][CH2:19]2)[CH:14]=[CH:15][C:16]=1[F:17].N1C=CC=CC=1>O>[F:10][C:11]1[CH:12]=[C:13]([C@@H:18]2[CH2:19][O:20][CH2:21][C@@H:22]3[C@H:24]([CH3:25])[O:26][C:1](=[O:5])[C:2](=[O:3])[N:23]23)[CH:14]=[CH:15][C:16]=1[F:17]

Participants

6

Reactant 4

HCID 1049PyridineHCID 6344DichloromethaneHCID 65578Oxalyl chlorideHCID 673752911-[(3R,5R)-5-(3,4-difluorophenyl)morpholin-3-yl]ethanol

Product 1

HCID 67372582(1S,6R,9aR)-6-(3,4-difluorophenyl)-1-methyltetrahydro-[1,4]oxazino[3,4-c][1,4]oxazine-3,4-dione

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Under ice-cooling, oxalyl chloride (417 μL) was added dropwise into a dichloromethane (8 mL) solution of 1-[(3R,5R)-5-(3,4-difluorophenyl)morpholin-3-yl]ethanol (424 mg) and pyridine (2 mL). Stirring was continued for 30 minutes at the same temperature. Water was added to the reaction solution, and the organic layer was partitioned, and the resultant was dried with magnesium sulfate, and the solvent was removed under a vacuum. The residue was purified with silica gel column chromatography (heptane/ethyl acetate 9/1→1/4), and the title compound (353 mg) was obtained. The physical property values are as follows.

Workup

  1. temperatureUnder ice-cooling
  2. customthe organic layer was partitioned
  3. dry with materialthe resultant was dried with magnesium sulfate
  4. customthe solvent was removed under a vacuum
  5. customThe residue was purified with silica gel column chromatography (heptane/ethyl acetate 9/1→1/4)

Sources & evidence

ORD record
ord-a3759d704d804696915004a8013d1d6a
Source dataset
uspto-grants-2011_08
Patent number
US08008293B2

Reaction notes

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