Phosphorus oxide (P4O10) → 1-(Chloromethyl)-7-ethyl-3,4-dihydroisoquinoline hydrochloride

Temperature

90 °C

Phosphorus pentoxide (15.85 g) was added to a solution of 2-chloro-N-[2-(4-ethylphenyl)ethyl]acetamide (7.87 g) in xylene (140 mL) under stirring at 90° C. over 5 minutes. The reaction mixture was heated at 120° C. and stirred for 2 hours. The reaction mixture was cooled to room temperature. The supernatant was removed and the residue was washed sequentially with toluene and ether. Crushed ice (150 g) was added to the residue, followed by stirring. A 20% aqueous sodium hydroxide solution was further added to the mixture to be a pH of 10 or higher, and the mixture was extracted with chloroform. The organic layer was collected, washed with water and saturated brine, and dried over anhydrous magnesium sulfate. To the organic layer was added a 4 M HCl/EtOAc solution (15 mL), and the mixture was concentrated under reduced pressure to obtain 1-(chloromethyl)-7-ethyl-3,4-dihydroisoquinoline hydrochloride (8.5 g).

1. temperatureThe reaction mixture was heated at 120° C.
2. stirringstirred for 2 hours
3. temperatureThe reaction mixture was cooled to room temperature
4. customThe supernatant was removed
5. washthe residue was washed sequentially with toluene and ether
6. additionCrushed ice (150 g) was added to the residue
7. stirringby stirring
8. additionA 20% aqueous sodium hydroxide solution was further added to the mixture
9. extractionhigher, and the mixture was extracted with chloroform
10. customThe organic layer was collected
11. washwashed with water and saturated brine
12. dry with materialdried over anhydrous magnesium sulfate
13. additionTo the organic layer was added a 4 M HCl/EtOAc solution (15 mL)
14. concentrationthe mixture was concentrated under reduced pressure

ORD record

ord-522f22ee46474d66bffb294e87509f37

Source dataset

uspto-grants-2012_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08263607B2