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

HRID 1802331Notes

Reaction equation

HRID 1802331 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

To a 1000-mL flask equipped with thermometer and addition funnel were added 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 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 between 10 to 30° C. The organic layer was separated, washed with saturated aqueous sodium chloride solution (80 mL), and then concentrated under reduced pressure. The resulting oil was crystallized from hexanes (100 mL), collected by filtration, washed with hexanes, and 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. customTo a 1000-mL flask equipped with thermometer and addition funnel
  2. temperaturewhile maintaining the temperature between −10 to −5° C
  3. temperaturewhile maintaining the temperature 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. washwashed with hexanes
  10. customdried in a vacuum oven overnight at 23° C.

Sources & evidence

ORD record
ord-b1d20462ee7f495eac7fa0fa30e45c40
Source dataset
uspto-grants-2013_01
Patent number
US08349870B2

Reaction notes

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