Benzyl Alcohol → 1-(3-(Benzyloxy)-2-fluoro-6-nitrophenyl)propan-2-one

HRID 454218Notes

Reaction equation

HRID 454218 reaction equation
[CH2:1]([OH:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].F[C:12]1[CH:17]=[CH:16][C:15]([N+:18]([O-:20])=[O:19])=[C:14]([CH2:21][C:22](OC)([O:24]C)[CH3:23])[C:13]=1[F:28]>CC(N(C)C)=O.Cl>[C:22]([CH2:21][C:14]1[C:13]([F:28])=[C:12]([O:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[CH:17]=[CH:16][C:15]=1[N+:18]([O-:20])=[O:19])(=[O:24])[CH3:23]

Participants

6

Reactant 3

HCID 244Benzyl AlcoholHCID 24758Sodium hydrideHCID 22030751HCID 22030751, compound

Product 1

HCID 112896631-(3-(Benzyloxy)-2-fluoro-6-nitrophenyl)propan-2-oneYield 56.3%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 31374DimethylacetamideSolvent2×

Procedure

To a solution of benzyl alcohol (221 mg, 2.05 mmol) in DMA (1.5 ml) was added 60% sodium hydride (82 mg, 2.05 mmol). The mixture was stirred for 1 hour at ambient temperature. A solution of 1,2-difluoro-3-(2,2-dimethoxypropyl)-4-nitrobenzene (534 mg, 2.05 mmol) in DMA (1.5 ml) was added and the mixture was stirred for 3 hours at ambient temperature. The mixture was diluted with 1N hydrochloric acid (10 ml) and extracted with ethyl acetate. The organic layer was evaporated and the residue was dissolved in THF (2 ml) and 6N hydrochloric acid (0.3 ml) was added. The mixture was stirred for 1 hour at ambient temperature and the solvents were removed under vacuum. The residue was partitioned between ethyl acetate and water. The organic layer was separated, washed with brine, dried (MgSO4) and evaporated. The solid was triturated with ether, filtered, washed with ether and dried under vacuum to give 3-acetylmethyl-1-benzyloxy-2-fluoro-4-nitrobenzene (350 mg, 56%).

Workup

  1. stirringthe mixture was stirred for 3 hours at ambient temperature
  2. extractionextracted with ethyl acetate
  3. customThe organic layer was evaporated
  4. dissolutionthe residue was dissolved in THF (2 ml)
  5. addition6N hydrochloric acid (0.3 ml) was added
  6. stirringThe mixture was stirred for 1 hour at ambient temperature
  7. customthe solvents were removed under vacuum
  8. customThe residue was partitioned between ethyl acetate and water
  9. customThe organic layer was separated
  10. washwashed with brine
  11. dry with materialdried (MgSO4)
  12. customevaporated
  13. customThe solid was triturated with ether
  14. filtrationfiltered
  15. washwashed with ether
  16. customdried under vacuum

Sources & evidence

ORD record
ord-cc308e52f2224c83b81cfba7fdc2d8aa
Source dataset
uspto-grants-2013_07
Patent number
US08492560B2

Reaction notes

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