Sodium Carbonate → Ethyl 4-[(2S,4R)-1-acetyl-2-methyl-4-({[(1-methylethyl)oxy]carbonyl}amino)-1,2,3,4-tetrahydro-6-quinolinyl]benzoate

Participants

Reaction Conditions

Reaction Steps

1-Methylethyl[(2S,4R)-1-acetyl-6-bromo-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl]carbamate (for a preparation see intermediate 100) (39.0 g, 106 mmol), {4-[(ethyloxy)carbonyl]phenyl}boronic acid (22.5 g, 116 mmol) and tetrakis(triphenylphosphine)palladium(0) (1.83 g, 1.584 mmol) were mixed in DME (430 mL) and the mixture treated with a 2M Na2CO3 aqueous solution (210 mL, 420 mmol). The resulting mixture was degassed under house vacuo with several quenches with nitrogen, stirred at 105° C. under nitrogen for approximately 6 h and then cooled to room temperature and partitioned between AcOEt and water. The two layers were separated and the aqueous phase was extracted with AcOEt. The combined organic phases were washed brine then were filtered through a 70 g silica cartridge, washing the cartridge with AcOEt. The combined filtrate and washings were concentrated in vacuovacuo. The residue was triturated with Et2O then filtered off to give ethyl 4-[(2S,4R)-1-acetyl-2-methyl-4-({[(1-methylethyl)oxy]carbonyl}amino)-1,2,3,4-tetrahydro-6-quinolinyl]benzoate (35.2 g, 80.56 mmol, 76%) as a grey solid. The mother liquors were concentrated in vacuo and the residue obtained triturated with Et2O. The solid formed was filtered off to give ethyl 4-[(2S,4R)-1-acetyl-2-methyl-4-({[(1-methylethyl)oxy]carbonyl}amino)-1,2,3,4-tetrahydro-6-quinolinyl]benzoate (5.96 g, 13.64 mmol, 13%) as a grey solid.

Provenance & Evidence