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 14), (39.0 g, 106 mmol), {4-[(ethyloxy)carbonyl]phenyl}boronic acid (22.5 g, 116 mmol) and tetrakis(triphenylphosphine)palladium(0) (1.83 g, 1.58 mmol) were mixed in DME (430 mL) and the resulting mixture was treated with aqueous Na2CO3 (2N, 210 mL, 420 mmol). The mixture was degassed under house vacuum with several quenches with nitrogen and then stirred at 105° C. under nitrogen for approximately 6 h before being allowed to cool to room temperature. The mixture was partitioned between EtOAc and water and the layers were separated. The aqueous phase was extracted with EtOAc and the combined organic phases were washed with brine. The organic phase was then filtered through a 70 g silica cartridge, washing the cartridge with EtOAc. The combined filtrate and washings were concentrated in vacuo. The residue was triturated with Et2O then filtered off. The solid obtained was air-dried to give 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 15) (35.2 g, 80.2 mmol, 76%) as a grey solid. The filtrate was concentrated in vacuo and the residue obtained triturated with Et2O (approximately 30 mL). The solid formed was isolated by filtration and air-dried, to give ethyl 4-[(2S,4R)-1-acetyl-2-methyl-4-({[(1-methylethyl)oxy]carbonyl}amino)-1,2,3,4-tetrahydro-6-quinolinyl]benzoate as a grey solid (5.96 g, 13.5 mmol, 13%). LCMS (formate, 2 min), Retention time 1.16 min, MH+=439

Provenance & Evidence