N,N'-Dimethylethylenediamine → Methyl 2-fluoro-4-(2-oxo-1(2H)-pyridinyl)benzoate

HRID 1271711Notes

Reaction equation

HRID 1271711 reaction equation
[CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[CH:8][C:7](Br)=[CH:6][C:5]=1[F:11].[OH:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=1.C([O-])([O-])=O.[K+].[K+].CNCCNC>[Cu]I.CCOC(C)=O.C1(C)C=CC=CC=1>[CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[CH:8][C:7]([N:15]2[CH:16]=[CH:17][CH:18]=[CH:19][C:14]2=[O:13])=[CH:6][C:5]=1[F:11]

Participants

8

Reactant 4

HCID 8070N,N'-DimethylethylenediamineHCID 11430Potassium CarbonateHCID 113453114-Bromo-2-fluoro-benzoic acid methyl esterHCID 178516071HCID 178516071, compound

Product 1

HCID 69146245Methyl 2-fluoro-4-(2-oxo-1(2H)-pyridinyl)benzoateYield 84.9%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 4-bromo-2-fluoro-benzoic acid methyl ester (1.17 g, 5.0 mmol), 2-hydroxypyridine (0.72 g, 7.5 mmol, 1.5 eq), K2CO3 (1.38 g, 10.0 mmol, 2.0 eq), CuI (0.48 g, 2.5 mmol, 0.5 eq), and N,N′-dimethylethylenediamine (0.22 mL, 2.6 mmol, 0.5 eq) was heated in refluxing toluene (6 mL) for 8 h. After cooling, EtOAc was added. The mixture was filtered through a pad of silica gel and rinsed with EtOAc. The desired fractions were concentrated in vacuo to give essentially pure 2-fluoro-4-(2-oxo-2H-pyridin-1-yl)-benzoic acid methyl ester (1.05 g, yield: 84%). 1H NMR (CDCl3) δ 8.07 (t, J=8.0 Hz, 1H), 7.14 (m, 1H), 7.33–7.27 (m, 3H), 6.64 (m, 1H), 6.28 (m, 1H), 3.96 (s, 3H) ppm. LC/MS (ESI) 248.05 (M+H), tR=2.05 min (10–90% MeOH in H2O with 10 mM NH4OAc in a 4-min run).

Workup

  1. temperaturewas heated
  2. temperatureAfter cooling
  3. filtrationThe mixture was filtered through a pad of silica gel
  4. washrinsed with EtOAc
  5. concentrationThe desired fractions were concentrated in vacuo

Sources & evidence

ORD record
ord-cc1f9c724dc1414fb0c878d17740c240
Source dataset
uspto-grants-2007_04
Patent number
US07205318B2

Reaction notes

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