Methanol → 3-Methyl-4-oxo-1-phenyl-7-trifluoromethyl-1,4-dihydro-[1,8]naphthyridine-2-carboxylic acid methyl ester

HRID 1887821Notes

Reaction equation

HRID 1887821 reaction equation
[CH3:1][O:2][C:3](=[O:27])[C:4]([N:6]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[C:7]1[C:12]([C:13](=[O:16])[CH2:14][CH3:15])=[CH:11][CH:10]=[C:9]([C:17]([F:20])([F:19])[F:18])[N:8]=1)=O.CO.C(=O)([O-])[O-].[K+].[K+]>O>[CH3:1][O:2][C:3]([C:4]1[N:6]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:7]2[C:12]([C:13](=[O:16])[C:14]=1[CH3:15])=[CH:11][CH:10]=[C:9]([C:17]([F:20])([F:19])[F:18])[N:8]=2)=[O:27]

Participants

5

Reactant 3

HCID 887MethanolHCID 11430Potassium CarbonateHCID 71208684N-phenyl-N-(3-propionyl-6-trifluoromethyl-pyridin-2-yl)-oxalamic acid methyl ester

Product 1

HCID 712084863-Methyl-4-oxo-1-phenyl-7-trifluoromethyl-1,4-dihydro-[1,8]naphthyridine-2-carboxylic acid methyl esterYield 53.6%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

In a 250 mL pear-shaped flask, N-phenyl-N-(3-propionyl-6-trifluoromethyl-pyridin-2-yl)-oxalamic acid methyl ester (1.74 g, 4.58 mmol) was combined with methanol (25 mL) to give a yellow solution. Potassium carbonate (3.8 g, 27.5 mmol) was added and the reaction mixture was refluxed for 2 hr. The reaction mixture was cooled, diluted with H2O (75 mL) and extracted with ethyl acetate (3×75 mL). The organic layers were combined, washed with brine (1×50 mL), dried over MgSO4, and concentrated in vacuo to give 1.7 g crude product as a yellow solid. The crude material was purified by flash chromatography (silica gel, 120 g, 20% to 50% ethyl acetate in hexanes) to give 3-methyl-4-oxo-1-phenyl-7-trifluoromethyl-1,4-dihydro-[1,8]naphthyridine-2-carboxylic acid methyl ester (0.89 g, 3.7%) as an off-white solid. 1H NMR (DMSO-d6) δ ppm 8.84 (d, J=8.2 Hz, 1H) 7.91 (d, J=8.2 Hz, 1H) 7.32-7.70 (m, 5H) 3.51 (s, 3H) 2.01 (s, 3H). MS calcd. for C18H13F3N2O3 [(M+H)+] 363.0, obsd. 363.0.

Workup

  1. customto give a yellow solution
  2. temperaturethe reaction mixture was refluxed for 2 hr
  3. temperatureThe reaction mixture was cooled
  4. extractionextracted with ethyl acetate (3×75 mL)
  5. washwashed with brine (1×50 mL)
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated in vacuo
  8. customto give 1.7 g crude product as a yellow solid
  9. customThe crude material was purified by flash chromatography (silica gel, 120 g, 20% to 50% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-fe48009d5562444a9d2674ba73ac7b98
Source dataset
uspto-grants-2013_08
Patent number
US08501732B2

Reaction notes

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