Hydrochloric Acid → 2-fluoro-N-[3-hydroxy-2-(7-methoxy-1-naphthyl)propyl]acetamide

HRID 2115585Notes

Reaction equation

HRID 2115585 reaction equation
Cl.[NH2:2][CH2:3][CH:4]([C:7]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([O:17][CH3:18])[CH:15]=2)[CH:10]=[CH:9][CH:8]=1)[CH2:5][OH:6].[F:19][CH2:20][C:21](OCC)=[O:22].[OH-].[Na+].Cl>FC(F)(F)CO.CO.O>[F:19][CH2:20][C:21]([NH:2][CH2:3][CH:4]([C:7]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([O:17][CH3:18])[CH:15]=2)[CH:10]=[CH:9][CH:8]=1)[CH2:5][OH:6])=[O:22]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 9988Ethyl fluoroacetateHCID 14798Sodium HydroxideHCID 685970113-Amino-2-(7-methoxy-1-naphthyl)-1-propanol hydrochloride

Product 1

HCID 236423072-fluoro-N-[3-hydroxy-2-(7-methoxy-1-naphthyl)propyl]acetamide

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolvent3×HCID 64092,2,2-TrifluoroethanolSolvent

Conditions

Temperature
40 °C

Procedure

The compound obtained in Step B (5.6 mmol), in the form of the base, is dissolved in 40 ml of 2,2,2-trifluoroethanol; ethyl fluoroacetate (10.3 mmol) is added and the mixture is refluxed for 12 hours. When the reaction is complete, the mixture is poured into water and the aqueous phase is extracted twice with 60 ml of ether; the organic phase is washed with water, dried and evaporated. The oil obtained is dissolved in 30 ml of methanol and 10 ml of water; sodium hydroxide (8.25 mmol) is added and the mixture is heated at 40° C. for 30 minutes. The mixture is then poured into water; the aqueous phase is neutralised with 15 ml of hydrochloric acid solution (1 M) and is then extracted twice with 60 ml of ether. The organic phase is washed with water, dried and evaporated. The oil obtained is precipitated from a mixture of ether and petroleum ether (40/60); the precipitate formed is filtered off under suction and then recrystallised from toluene to yield the title compound in the form of a white solid.

Workup

  1. temperaturethe mixture is refluxed for 12 hours
  2. extractionthe aqueous phase is extracted twice with 60 ml of ether
  3. washthe organic phase is washed with water
  4. customdried
  5. customevaporated
  6. customThe oil obtained
  7. extractionis then extracted twice with 60 ml of ether
  8. washThe organic phase is washed with water
  9. customdried
  10. customevaporated
  11. customThe oil obtained
  12. customis precipitated from a mixture of ether and petroleum ether (40/60)
  13. customthe precipitate formed
  14. filtrationis filtered off under suction
  15. customrecrystallised from toluene

Sources & evidence

ORD record
ord-ccdd1cca95914b22b3d80af256d52ac2
Source dataset
uspto-grants-2008_10
Patent number
US07435850B2

Reaction notes

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