Hydrochloric Acid → 8-Fluoro-2-formyl-5-methoxytetralone

HRID 374659Notes

Reaction equation

HRID 374659 reaction equation
[H-].[Na+].[CH:3](OCC)=[O:4].[CH3:8][O:9][C:10]1[CH:19]=[CH:18][C:17]([F:20])=[C:16]2[C:11]=1[CH2:12][CH2:13][CH2:14][C:15]2=[O:21].Cl>C1COCC1.O.CO>[F:20][C:17]1[CH:18]=[CH:19][C:10]([O:9][CH3:8])=[C:11]2[C:16]=1[C:15](=[O:21])[CH:14]([CH:3]=[O:4])[CH2:13][CH2:12]2

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 8025Ethyl formateHCID 24758Sodium hydrideHCID 108563538-Fluoro-3,4-dihydro-5-methoxy-1(2H)-naphthalenone

Product 1

HCID 189969618-Fluoro-2-formyl-5-methoxytetraloneYield 113.1%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent2×

Procedure

Sodium hydride (12.7 g) (50% dispersion, washed with hexane) was suspended in dry THF under nitrogen. Ethyl formate (27 g) was added and the mixture was stirred for 20 minutes in an ice/water bath. 5-Methoxy-8-fluoro-1-tetralone (J. Med. Chem. (1973) 1003) (17 g) dissolved in THF was added and the mixture was allowed to warm to room temperature. The mixture was stirred under nitrogen for 24 hours. Methanol was added followed by water. The mixture was poured into water, acidified with conc. HCl (aq) and extracted into CHCl3. The organic phase was dried (MgSO4), filtered and concentrated to give a dark oil (22 g) which solidified on standing. This material was recrystallised from ethyl acetate/hexane to give the above compound, m.p. 66°-68° C.

Workup

  1. additionwas added
  2. stirringThe mixture was stirred under nitrogen for 24 hours
  3. extractionextracted into CHCl3
  4. dry with materialThe organic phase was dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-48af8b61367041eda8da53877cf5afc3
Source dataset
uspto-grants-1996_01
Patent number
US05480873

Reaction notes

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