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

HRID 75169Notes

Reaction equation

HRID 75169 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 1 L flask equipped with a thermometer and addition funnel was 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 methyl magnesium bromide (3.0 M in tetrahydrofuran, 120 mL, 0.36 mmol) was added dropwise while maintaining the temperature between −10 and −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 and 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 1 L flask equipped with a thermometer and addition funnel
  2. temperaturewhile maintaining the temperature between −10 and −5° C
  3. temperaturewhile maintaining the temperature between 10 and 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-fe2a8ebf4e064c41a6a3def2d333218c
Source dataset
uspto-grants-2014_09
Patent number
US08835427B2

Reaction notes

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