Methanol → ethyl 4-((2S,4R)-1-acetyl-4-amino-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)benzoate

Participants

Reaction Conditions

Reaction Steps

Ethyl 4-[(2S,4R)-1-acetyl-2-methyl-4-({[(1-methylethyl)oxy]carbonyl}amino)-1,2,3,4-tetrahydro-6-quinolinyl]benzoate (for a preparation see intermediate 85) (8.90 g, 20.30 mmol) was added to a suspension of aluminium chloride (10.3 g, 77 mmol) in DCM (160 mL) cooled with an ice/water bath. The temperature rose from 0° C. to approximately 6° C. after the addition. The resulting mixture was stirred at approximately 0° C. for 20 min, and then treated with a solution of methanol (18 mL) and triethylamine (34 mL, 245 mmol) over approximately 30 sec. The resulting mixture was stirred at 0° C. for approximately 30 min, and then partitioned between AcOEt and a saturated NaHCO3 aqueous solution. The same reaction was done in parallel, using 0.89 g (2.030 mmol) of ethyl 4-[(2S,4R)-1-acetyl-2-methyl-4-({[(1-methylethyl)oxy]carbonyl}amino)-1,2,3,4-tetrahydro-6-quinolinyl]benzoate (for a preparation see intermediate 85), 1.03 g (7.72 mmol) of aluminium chloride, 3.4 mL (24.53 mmol) of triethylamine, 16 mL of DCM and 1.3 mL of MeOH. The products of both reactions were combined at this stage and the resulting mixture was stirred at room temperature for approximately 10 min (total volume: approximately 1 L). The mixture was filtered through celite, the insoluble residue was washed with AcOEt and a saturated NaHCO3 aqueous solution and the layers were separated. The aqueous phase was extracted with AcOEt and the combined organic phases were washed with brine, dried using an hydrophobic frit and concentrated in vacuo to give ethyl 4-[(2S,4R)-1-acetyl-4-amino-2-methyl-1,2,3,4-tetrahydro-6-quinolinyl]benzoate (6.6 g, 84%—allowing for the addition of the parallel experiment) as a cream solid.

Provenance & Evidence