Diphosgene → 6-fluoro-1-(4-methoxy-benzyl)-1H-pyrido[2,3-d][1,3]oxazine-2,4-dione

HRID 901249Notes

Reaction equation

HRID 901249 reaction equation
ClC(OC(Cl)(Cl)Cl)=[O:3].[CH2:9]([O:11][C:12](=[O:30])[C:13]1[CH:18]=[C:17]([F:19])[CH:16]=[N:15][C:14]=1[NH:20][CH2:21][C:22]1[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][CH:23]=1)C>O1CCOCC1>[F:19][C:17]1[CH:16]=[N:15][C:14]2[N:20]([CH2:21][C:22]3[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][CH:23]=3)[C:9](=[O:3])[O:11][C:12](=[O:30])[C:13]=2[CH:18]=1

Participants

4

Reactant 2

HCID 10426DiphosgeneHCID 589458085-Fluoro-2-(4-methoxy-benzylamino)-nicotinic acid ethyl ester

Product 1

HCID 596996236-fluoro-1-(4-methoxy-benzyl)-1H-pyrido[2,3-d][1,3]oxazine-2,4-dioneYield 90.2%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

Trichloromethyl chloroformate (11.41 mL, 94.63 mmol) was added slowly to a solution of 5-fluoro-2-(4-methoxy-benzylamino)-nicotinic acid ethyl ester (68) (24 g, 78.86 mmol) in dioxane and refluxed for 4 h under nitrogen atmosphere. The solution was cooled and the solvent was removed under vacuum. The residue was recrystallized by ether to yield 21.5 g (90%) of 6-fluoro-1-(4-methoxy-benzyl)-1H-pyrido[2,3-d][1,3]oxazine-2,4-dione (69) as white solids. MP: 143° C.; 1H-NMR (DMSO-d6): δ 3.71 (s, 3H), 5.27 (s, 2H), 6.85 (m, 2H), 7.35 (m, 2H), 8.40 (dd, J=2.8, 6.8 Hz, 1H), 8.82 (d, J=2.8 Hz, 1H); EIMS: 303 (M+1).

Workup

  1. temperaturerefluxed for 4 h under nitrogen atmosphere
  2. temperatureThe solution was cooled
  3. customthe solvent was removed under vacuum
  4. customThe residue was recrystallized by ether

Sources & evidence

ORD record
ord-4600ad18a53441519cc1ae7be765b4e8
Source dataset
uspto-grants-2008_04
Patent number
US07361760B2

Reaction notes

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