Sodium hydride → HCID 59987430, compound

HRID 658484Notes

Reaction equation

HRID 658484 reaction equation
[CH3:1][O:2][C:3](=[O:11])[C:4]1[CH:9]=[C:8]([OH:10])[CH:7]=[N:6][CH:5]=1.[H-].[Na+].F[C:15]1[C:20]([F:21])=[C:19]([N+:22]([O-:24])=[O:23])[CH:18]=[CH:17][CH:16]=1>CN(C=O)C>[CH3:1][O:2][C:3](=[O:11])[C:4]1[CH:9]=[C:8]([O:10][C:16]2[CH:17]=[CH:18][C:19]([N+:22]([O-:24])=[O:23])=[C:20]([F:21])[CH:15]=2)[CH:7]=[N:6][CH:5]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 813351,2-Difluoro-3-nitrobenzeneHCID 354317Methyl 5-hydroxypyridine-3-carboxylate

Product 1

HCID 59987430HCID 59987430, compoundYield 28%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To an ice bath cooled solution of 5-hydroxynicotinic acid methyl ester (5.00 g, 32.65 mmol) in DMF (20 mL) was added sodium hydride (0.78 g, 32.65 mmol). The reaction mixture was stirred at room temperature for 2 hours, and 2,3-difluoro-4-nitrobenzene (5.12 g, 29.68 mmol) was added, and the reaction mixture was stirred at room temperature. After 3 hours the solvent was removed under reduced pressure, and the residue was partitioned between EtOAC (300 mL) and H2O (150 mL). The aqueous layer was extracted with EtOAc (100 mL), and the combined organic layers were dried over Na2SO4, filtered, and the filtrate removed under reduced pressure. The crude product was purified by column chromatography eluted with 50 to 75% EtOAc/Hex to give 2.4 g (28%) of 5-(4-nitro-3-fluorophenoxy)nicotinic acid methyl ester. 1H-NMR (CD3OD) δ 9.05 (d, J=1.8 Hz, 1H), 8.70 (d, J=2.7 Hz, 1H), 8.31 (dd, J=2.4, 10.5 Hz, 1H), 8.15-8.14 (m, 1H), 9.06 (dd, J=1.5, 2.1 Hz, 1H), 7.40 (dd, J=8.1, 9.0 Hz, 1H), 3.97 (s, 3H); MS LC-MS [M+H]+=293.1; RT=3.15 min.

Workup

  1. stirringthe reaction mixture was stirred at room temperature
  2. customAfter 3 hours the solvent was removed under reduced pressure
  3. customthe residue was partitioned between EtOAC (300 mL) and H2O (150 mL)
  4. extractionThe aqueous layer was extracted with EtOAc (100 mL)
  5. dry with materialthe combined organic layers were dried over Na2SO4
  6. filtrationfiltered
  7. customthe filtrate removed under reduced pressure
  8. customThe crude product was purified by column chromatography
  9. washeluted with 50 to 75% EtOAc/Hex

Sources & evidence

ORD record
ord-acd0be242fca4d35b5bdd02dabc0b9ba
Source dataset
uspto-grants-2011_12
Patent number
US08076488B2

Reaction notes

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