Methanol → (2S,4R)-1-acetyl-6-[3,4-bis(methyloxy)phenyl]-2-methyl-1,2,3,4-tetrahydro-4-quinolinamine

Participants

Reaction Conditions

Reaction Steps

1-Methylethyl {(2S,4R)-1-acetyl-6-[3,4-bis(methyloxy)phenyl]-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl}carbamate (for a preparation see intermediate 95) (327 mg, 0.767 mmol) was added to a cold (ice bath) suspension of aluminium chloride (388 mg, 2.91 mmol) in dichloromethane (DCM) (4 mL). The reaction was stirred at approximately 0° C. for 30 min then an extra amount of aluminium chloride (102 mg, 0.767 mmol) was added and the resulting mixture was stirred at approximately 0° C. for 30 min. Aluminium chloride (102 mg, 0.767 mmol) was further added and the resulting mixture was stirred at approximately 0° C. for 30 min. Further Aluminium chloride (102 mg, 0.767 mmol) was added and the resulting mixture was stirred at approximately 0° C. for 30 min. The reaction mixture was then treated with a solution of methanol (0.884 mL) and triethylamine (2.312 mL, 16.59 mmol) and the resulting mixture was stirred further at approximately 0° C. for 20 min then was partitioned between EtOAc (35 mL) and a saturated NaHCO3 aqueous solution (35 mL). The reaction mixture was then filtered through celite and the insoluble were washed with EtOAc (25 mL) and NaHCO3 (25 mL). The filtered aluminum residues were suspended in MeOH and sonicated. The resulting suspension was filtered and the filtrate was concentrated in vacuovacuo. The white solid residue was loaded onto a 10 g SCX cartridge and eluted with MeOH and then with 2M NH3 in MeOH. The methanol fractions were combined and concentrated in vacuo to give (2S,4R)-1-acetyl-6-[3,4-bis(methyloxy)phenyl]-2-methyl-1,2,3,4-tetrahydro-4-quinolinamine (103 mg, 39%) and the combined ammonia fractions were combined to give (2S,4R)-1-acetyl-6-[3,4-bis(methyloxy)phenyl]-2-methyl-1,2,3,4-tetrahydro-4-quinolinamine (71 mg, 27%).

Provenance & Evidence