Sodium → 1-(2-Fluoro-3-methoxy-6-nitrophenyl)propan-2-one

HRID 454220Notes

Reaction equation

HRID 454220 reaction equation
[CH3:1][O-:2].[Na+].[Na].F[C:6]1[CH:11]=[CH:10][C:9]([N+:12]([O-:14])=[O:13])=[C:8]([CH2:15][C:16]([O:20]C)(OC)[CH3:17])[C:7]=1[F:22]>CO>[C:16]([CH2:15][C:8]1[C:7]([F:22])=[C:6]([O:2][CH3:1])[CH:11]=[CH:10][C:9]=1[N+:12]([O-:14])=[O:13])(=[O:20])[CH3:17]

Participants

5

Reactant 3

HCID 5360545SodiumHCID 10942334Sodium MethoxideHCID 22030751HCID 22030751, compound

Product 1

HCID 220307431-(2-Fluoro-3-methoxy-6-nitrophenyl)propan-2-oneYield 90%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Conditions

Temperature
5 °C

Procedure

A solution of sodium methoxide (freshly prepared from sodium (1.71 g) and methanol (35 ml)) was added to a solution of 1,2-difluoro-3-(2,2-dimethoxypropyl)-4-nitrobenzene (16.2 g, 62 mmol), (prepared as described above), in methanol (200 ml) cooled at 5° C. The mixture was left to warm to ambient temperature and was stirred for 3 days. The volatiles were removed under vacuum and the residue was partitioned between ethyl acetate and 2N hydrochloric acid (1 ml). The organic layer was concentrated to a total volume of 100 ml and THF (100 ml) and 6N hydrochloric acid (25 ml) were added. The mixture was stirred for 1 hour at ambient temperature. The volatiles were removed under vacuum and the residue was partitioned between ethyl acetate and water. The organic layer was separated, washed with water, brine, dried (MgSO4) and evaporated. The residue was purified by column chromatography eluting with ethyl acetate/petroleum ether (3/7) to give 3-acetylmethyl-2-fluoro-1-methoxy-4-nitrobenzene (12.7 g, 90%).

Workup

  1. waitThe mixture was left
  2. temperatureto warm to ambient temperature
  3. customThe volatiles were removed under vacuum
  4. customthe residue was partitioned between ethyl acetate and 2N hydrochloric acid (1 ml)
  5. concentrationThe organic layer was concentrated to a total volume of 100 ml and THF (100 ml) and 6N hydrochloric acid (25 ml)
  6. additionwere added
  7. stirringThe mixture was stirred for 1 hour at ambient temperature
  8. customThe volatiles were removed under vacuum
  9. customthe residue was partitioned between ethyl acetate and water
  10. customThe organic layer was separated
  11. washwashed with water, brine
  12. dry with materialdried (MgSO4)
  13. customevaporated
  14. customThe residue was purified by column chromatography
  15. washeluting with ethyl acetate/petroleum ether (3/7)

Sources & evidence

ORD record
ord-9442689db3e0417b98736ee3f4ee3471
Source dataset
uspto-grants-2013_07
Patent number
US08492560B2

Reaction notes

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