Hydrochloric Acid → 3-Bromo-1-[2-(methoxymethyl)-4-nitrophenyl]pyridin-2(1H)-one

HRID 2405013Notes

Reaction equation

HRID 2405013 reaction equation
[Br:1][C:2]1[C:3](=[O:8])[NH:4][CH:5]=[CH:6][CH:7]=1.C([O-])(C)(C)C.[K+].F[C:16]1[CH:21]=[CH:20][C:19]([N+:22]([O-:24])=[O:23])=[CH:18][C:17]=1[CH2:25][O:26][CH3:27].Cl>CN1CCCC1=O>[Br:1][C:2]1[C:3](=[O:8])[N:4]([C:16]2[CH:21]=[CH:20][C:19]([N+:22]([O-:24])=[O:23])=[CH:18][C:17]=2[CH2:25][O:26][CH3:27])[CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8185493-Bromo-2-hydroxypyridineHCID 23665647Potassium tert-butoxideHCID 594102191-Fluoro-2-(methoxymethyl)-4-nitrobenzene

Product 1

HCID 594101973-Bromo-1-[2-(methoxymethyl)-4-nitrophenyl]pyridin-2(1H)-one

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

Under argon, 44.2 g (85% purity, 216 mmol) of 3-bromopyridone in 450 ml of N-methylpyrrolidone were introduced as initial charge, and 29.1 g of potassium tert-butanolate (259 mmol) were added in portions such that the temperature remained below 30° C. The mixture was stirred for 1 h and then 40 g (216 mmol) of 1-fluoro-2-(methoxymethyl)-4-nitrobenzene were added. The reaction mixture was stirred for 4 h at 80° C., cooled to RT and stirred into an ice/water mixture. The pH was adjusted to pH=4 with semi-concentrated hydrochloric acid, the mixture was extracted with ethyl acetate, and the organic phase was dried over sodium sulphate, filtered and evaporated to dryness on a rotary evaporator. The residue was dissolved in 2 l of dichloromethane, absorbed on five times the amount of silica gel and chromatographically purified on silica gel with ethyl acetate:dichloromethane 3:97 and 5:95. The product fractions were evaporated to dryness on a rotary evaporator and the residue was dried in vacuo. This gave 55 g (73%) of the desired product.

Workup

  1. additionas initial charge
  2. customremained below 30° C
  3. stirringThe reaction mixture was stirred for 4 h at 80° C.
  4. extractionthe mixture was extracted with ethyl acetate
  5. dry with materialthe organic phase was dried over sodium sulphate
  6. filtrationfiltered
  7. customevaporated to dryness on a rotary evaporator
  8. dissolutionThe residue was dissolved in 2 l of dichloromethane
  9. customabsorbed on five times the amount of silica gel
  10. customchromatographically purified on silica gel with ethyl acetate:dichloromethane 3:97 and 5:95
  11. customThe product fractions were evaporated to dryness on a rotary evaporator
  12. customthe residue was dried in vacuo

Sources & evidence

ORD record
ord-ec8afd7f26d947e28e844de4d785c48b
Source dataset
uspto-grants-2014_08
Patent number
US08802860B2

Reaction notes

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