Methanol → 7-Chloro-3,4-dihydroisoquinolin-1(2H)-one

HRID 1843819Notes

Reaction equation

HRID 1843819 reaction equation
O=P12OP3(OP(OP(O3)(O1)=O)(=O)O2)=O.C([O:17][C:18](=O)[NH:19][CH2:20][CH2:21][C:22]1[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][CH:23]=1)C.CO>O=P(Cl)(Cl)Cl.C(Cl)Cl>[Cl:28][C:25]1[CH:26]=[C:27]2[C:22]([CH2:21][CH2:20][NH:19][C:18]2=[O:17])=[CH:23][CH:24]=1

Participants

6

Reactant 3

HCID 887MethanolHCID 14812Phosphorus oxide (P4O10)HCID 15405334ethyl N-[2-(4-chlorophenyl)ethyl]carbamate

Product 1

HCID 186723977-Chloro-3,4-dihydroisoquinolin-1(2H)-oneYield 25,095.9%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 24813Phosphorus oxychlorideSolvent

Procedure

P2O5 (3.1 g, 0.0495 mmol) was added to a stirred solution of [2-(4-chloro-phenyl)-ethyl]-carbamic acid ethyl ester (2.5 g, 0.01097 mmol) in POCl3 (10 mL) The resulting mixture was heated to reflux for 3 hours. The reaction was monitored by TLC (10% methanol in DCM). The reaction mixture was cooled to room temperature and concentrated under reduced pressure. The concentrate was quenched with chilled water, basified with NaHCO3 solution and extracted with ethylacetate. The organic layer was washed with water, brine solution, dried over Na2SO4 and concentrated under reduced pressure. Purification by column chromatography on silica gel (10% methanol in CHCl3) afforded 500 mg of the product (26.3% yield).

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 3 hours
  3. concentrationconcentrated under reduced pressure
  4. customThe concentrate was quenched with chilled water
  5. extractionextracted with ethylacetate
  6. washThe organic layer was washed with water, brine solution
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated under reduced pressure
  9. customPurification by column chromatography on silica gel (10% methanol in CHCl3)

Sources & evidence

ORD record
ord-2b00c07b8df449f0af710961f22bf424
Source dataset
uspto-grants-2015_02
Patent number
US08946260B2

Reaction notes

Loading…