Dimethylformamide → 2-Bromo-5-[(4-fluorophenyl)methyl]-3-nitropyridine

HRID 2364194Notes

Reaction equation

HRID 2364194 reaction equation
P(Br)(Br)([Br:3])=O.[F:6][C:7]1[CH:12]=[CH:11][C:10]([CH2:13][C:14]2[CH:15]=[C:16]([N+:21]([O-:23])=[O:22])[C:17](=O)[NH:18][CH:19]=2)=[CH:9][CH:8]=1.CN(C=O)C.[OH-].[Na+]>C1(C)C=CC=CC=1.O>[Br:3][C:17]1[C:16]([N+:21]([O-:23])=[O:22])=[CH:15][C:14]([CH2:13][C:10]2[CH:11]=[CH:12][C:7]([F:6])=[CH:8][CH:9]=2)=[CH:19][N:18]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 14798Sodium HydroxideHCID 24613Phosphorus oxybromideHCID 573548755-[(4-Fluorophenyl)methyl]-3-nitropyridin-2(1H)-one

Product 1

HCID 573548762-Bromo-5-[(4-fluorophenyl)methyl]-3-nitropyridine

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1140TolueneSolvent2×

Procedure

A solution of POBr3 (227 g, 0.79 mol) in toluene (900 mL) was added slowly to a stirred suspension of 5-[(4-fluorophenyl)methyl]-3-nitro-2(1H)-pyridinone (179 g, 0.72 mol) in toluene (900 mL). The mixture was heated to reflux; then cooled to rt and DMF (56 mL, 0.72 mol) was added slowly; the mixture was again heated to reflux and then allowed to cool to rt overnight. After cooling the mixture in an ice-bath, water (500 mL) was added slowly followed by dropwise addition 4 N NaOH (450 mL, 1.76 mol). All insoluble material was removed by filtration and the two liquid phases were separated. The organic layer was concentrated at reduced pressure to afford the product as a beige solid: 1H NMR (d6-DMSO) δ 8.62 (1H, d, J=2 Hz), 8.37 (1H, d, J=2 Hz), 7.33 (2H, m), 7.12 (2H, m), 4.05 (2H, s); ES+ MS: 313 (M+H+, 100), 311 (M+H+, 100).

Workup

  1. temperatureThe mixture was heated to reflux
  2. temperaturethe mixture was again heated
  3. temperatureto reflux
  4. temperatureto cool to rt overnight
  5. temperatureAfter cooling the mixture in an ice-bath
  6. customAll insoluble material was removed by filtration
  7. customthe two liquid phases were separated
  8. concentrationThe organic layer was concentrated at reduced pressure

Sources & evidence

ORD record
ord-c77111b56244465f8cd6eca5133eca83
Source dataset
uspto-grants-2014_04
Patent number
US08691991B2

Reaction notes

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