Hydrochloric Acid → 1-[5-(2,6-Difluorophenyl)-4,5-dihydro-1,2-oxazol-3-yl]ethanone

HRID 1916439Notes

Reaction equation

HRID 1916439 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[CH:9]1[O:13][N:12]=[C:11]([C:14](N(C)C)=[O:15])[CH2:10]1.[C:19]1(C)C=CC=CC=1.C[Mg]Br.Cl>O>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[CH:9]1[O:13][N:12]=[C:11]([C:14](=[O:15])[CH3:19])[CH2:10]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 1140TolueneHCID 666182295-(2,6-Difluorophenyl)-N,N-dimethyl-4,5-dihydroisoxazole-3-carboxamide3×HCID 178418573HCID 178418573, compound

Product 1

HCID 666184491-[5-(2,6-Difluorophenyl)-4,5-dihydro-1,2-oxazol-3-yl]ethanone

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
-5 °C

Procedure

A 1000-mL flask equipped with thermometer and addition funnel was charged with 5-(2,6-difluorophenyl)-4,5-dihydro-N,N-dimethyl-3-isoxazolecarboxamide (i.e. the product of Step A) (80.0 g, 0.31 mol) and toluene (320 mL). The reaction mixture was cooled to −5° C., and a solution of methyl magnesium bromide (3.0 M in tetrahydrofuran, 120 mL, 0.36 mmol) was added dropwise while maintaining the reaction temperature between −10 to −5° C. When gas chromatography analysis of the reaction mixture showed about 2% of 5-(2,6-difluorophenyl)-4,5-dihydro-N,N-dimethyl-3-isoxazolecarboxamide remaining, the reaction mixture was poured into a stirred solution of concentrated hydrochloric acid (80 mL) and water (320 mL) while maintaining the temperature of the mixture between 10 to 30° C. The organic layer was separated, washed with saturated aqueous sodium chloride solution (80 mL) and concentrated under reduced pressure. The resulting oil was crystallized from hexanes (100 mL) and collected by filtration washing with hexanes. The resulting solid was dried in a vacuum oven overnight at 23° C. to provide the title compound as a waxy, off-white solid (65 g), melting at 47-50° C.

Workup

  1. customA 1000-mL flask equipped with thermometer and addition funnel
  2. temperaturewhile maintaining the reaction temperature between −10 to −5° C
  3. temperaturewhile maintaining the temperature of the mixture between 10 to 30° C
  4. customThe organic layer was separated
  5. washwashed with saturated aqueous sodium chloride solution (80 mL)
  6. concentrationconcentrated under reduced pressure
  7. customThe resulting oil was crystallized from hexanes (100 mL)
  8. filtrationcollected by filtration
  9. washwashing with hexanes
  10. customThe resulting solid was dried in a vacuum oven overnight at 23° C.

Sources & evidence

ORD record
ord-2aa3078f628f447882c74c80616dae2c
Source dataset
uspto-grants-2013_12
Patent number
US08618137B2

Reaction notes

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