Methylamine → Ethyl 4-hydroxy-1-methyl-2-oxo-7-(trifluoromethyl)-1,2-dihydro-1,8-naphthyridine-3-carboxylate

HRID 1801985Notes

Reaction equation

HRID 1801985 reaction equation
[CH3:1][NH:2][C:3]1[N:12]=[C:11]([C:13]([F:16])([F:15])[F:14])[CH:10]=[CH:9][C:4]=1[C:5](OC)=[O:6].ClC1N=C(C(F)(F)F)C=C[C:19]=1[C:20](OC)=[O:21].[C:32]([O-:35])([O-])=[O:33].[K+].[K+].CN.[CH2:40]1COC[CH2:41]1>>[OH:6][C:5]1[C:4]2[C:3](=[N:12][C:11]([C:13]([F:14])([F:15])[F:16])=[CH:10][CH:9]=2)[N:2]([CH3:1])[C:20](=[O:21])[C:19]=1[C:32]([O:35][CH2:40][CH3:41])=[O:33]

Participants

6

Reactant 5

HCID 6329MethylamineHCID 8028Tetrahydrofuran2×HCID 11430Potassium CarbonateHCID 46311111Methyl 2-chloro-6-(trifluoromethyl)pyridine-3-carboxylateHCID 57671595Methyl 2-(methylamino)-6-(trifluoromethyl)nicotinate

Product 1

HCID 57671568Ethyl 4-hydroxy-1-methyl-2-oxo-7-(trifluoromethyl)-1,2-dihydro-1,8-naphthyridine-3-carboxylate

Procedure

Methyl 2-(methylamino)-6-(trifluoromethyl)nicotinate. A mixture of methyl 2-chloro-6-(trifluoromethyl)nicotinate (3.82 g) and K2CO3 (5.6 g, 40 mmol) in THF (25 mL) was stirred under nitrogen for 15 minutes. To the mixture was added a 2M solution of methylamine in THF (10 mL, 20 mmol) and stirring was continued for 63 hours. The reaction mixture was filtered over Celite® and the filtrate was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (DCM) to give the title compound. MS (ESI, pos. ion) m/z: 235 (M+1).

Workup

  1. stirringstirring
  2. waitwas continued for 63 hours
  3. filtrationThe reaction mixture was filtered over Celite®
  4. customthe filtrate was evaporated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (DCM)

Sources & evidence

ORD record
ord-28a75fa585ac463898d8aa56ead1908f
Source dataset
uspto-grants-2013_01
Patent number
US08349868B2

Reaction notes

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