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

Temperature

0 °C

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%).

1. stirringthe resulting mixture was stirred at approximately 0° C. for 30 min
2. stirringthe resulting mixture was stirred at approximately 0° C. for 30 min
3. stirringthe resulting mixture was stirred at approximately 0° C. for 30 min
4. stirringthe resulting mixture was stirred further at approximately 0° C. for 20 min
5. customthen was partitioned between EtOAc (35 mL)
6. filtrationThe reaction mixture was then filtered through celite
7. washthe insoluble were washed with EtOAc (25 mL) and NaHCO3 (25 mL)
8. customsonicated
9. filtrationThe resulting suspension was filtered
10. concentrationthe filtrate was concentrated in vacuovacuo
11. washeluted with MeOH
12. concentrationconcentrated in vacuo

ORD record

ord-febb7994d62a463089670e2aded38db2

Source dataset

uspto-grants-2013_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08580957B2