3-chloro-N-(2-fluorophenyl)propanamide → 8-Fluoro-1,2,3,4-tetrahydroquinolin-2-one

HRID 530331Notes

Reaction equation

HRID 530331 reaction equation
Cl[CH2:2][CH2:3][C:4]([NH:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[F:13])=[O:5].[Cl-].[Al+3].[Cl-].[Cl-]>>[F:13][C:8]1[CH:9]=[CH:10][CH:11]=[C:12]2[C:7]=1[NH:6][C:4](=[O:5])[CH2:3][CH2:2]2

Participants

3

Reactant 2

HCID 42560293-chloro-N-(2-fluorophenyl)propanamideHCID 6451240Aluminum(III) Chloride

Product 1

HCID 151448738-Fluoro-1,2,3,4-tetrahydroquinolin-2-oneYield 70.8%

Conditions

Temperature
160 °C

Procedure

A flame-dried 50-mL flask equipped with a magnetic stirring bar was charged with 3-chloro-N-(2-fluoro-phenyl)-propionamide (5.33 g, 26.5 mmol) and aluminium chloride (5.30 g, 39.7 mmol). In a pre-heated oil bath, the flask was heated at 160° C. for 1.5 hr. After cooling to room temperature, the mixture was treated with ice-water slowly and extracted with EtOAc. The organic layer was washed with water and brine in sequence, dried over anhy. Na2SO4, filtered, and concentrated in vacuo. The resulting residue was then purified by flash chromatography (silica gel, 30% ethyl acetate in hexane) to afford title compound (3.1 g, 70% yield) as a solid. MS: 166.0 (M+H)+.

Workup

  1. customA flame-dried 50-mL flask equipped with a magnetic stirring bar
  2. temperatureAfter cooling to room temperature
  3. extractionextracted with EtOAc
  4. washThe organic layer was washed with water and brine in sequence
  5. customdried over anhy
  6. filtrationNa2SO4, filtered
  7. concentrationconcentrated in vacuo
  8. customThe resulting residue was then purified by flash chromatography (silica gel, 30% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-e16845dd581e489eb0a4ee65399da6b9
Source dataset
uspto-grants-2016_05
Patent number
US09353081B2

Reaction notes

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