Ammonia → 6-chloro-3-methyl-3,4-dihydro-2H-isoquinolin-1-one

HRID 2277585Notes

Reaction equation

HRID 2277585 reaction equation
C[O:2][C:3](=O)[NH:4][CH:5]([CH3:14])[CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([Cl:13])[CH:8]=1.N>>[Cl:13][C:9]1[CH:8]=[C:7]2[C:12](=[CH:11][CH:10]=1)[C:3](=[O:2])[NH:4][CH:5]([CH3:14])[CH2:6]2

Participants

3

Reactant 2

HCID 222AmmoniaHCID 86685920[2-(3-Chloro-phenyl)-1-methyl-ethyl]-carbamic acid methyl ester

Product 1

HCID 866859216-chloro-3-methyl-3,4-dihydro-2H-isoquinolin-1-oneYield 26%

Conditions

Temperature
120 °C

Procedure

Under N2 protection, a mixture of [2-(3-chloro-phenyl)-1-methyl-ethyl]-carbamic acid methyl ester (1.2 g, 5.3 mmol) and PPA (polyphosphoric acid) (10 g) in a 100 mL round bottom flask was stirred at 120° C. for 2 hours. After cooling to room temperature, the reaction mixture was treated with ice-water and aqueous ammonia solution to adjust the pH to 8. The mixture was then extracted with ethyl acetate and the organic layer was washed with brine, dried over anhy. Na2SO4, filtered and concentrated in vacuo. The crude product obtained was further washed with ether to give 6-chloro-3-methyl-3,4-dihydro-2H-isoquinolin-1-one (0.27 g, 26%) (intermediate A-3-1) as a white solid. MS: 196.1 (M+H+). The ether filtrate was concentrated under reduced pressure and purified by flash chromatography to afford 8-chloro-3-methyl-3,4-dihydro-2H-isoquinolin-1-one (intermediate A-3-2) (54 mg, 5.2%) as a white solid. MS: 196.1 (M+H+).

Workup

  1. temperatureAfter cooling to room temperature
  2. extractionThe mixture was then extracted with ethyl acetate
  3. washthe organic layer was washed with brine
  4. customdried over anhy
  5. filtrationNa2SO4, filtered
  6. concentrationconcentrated in vacuo
  7. customThe crude product obtained
  8. washwas further washed with ether

Sources & evidence

ORD record
ord-a77066daff1f4a99b8ec2e59a143ee0f
Source dataset
uspto-grants-2015_09
Patent number
US09133158B2

Reaction notes

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