Citric Acid → 1,1-dimethylethyl [(cis)-2-methyl-6-(4-methyl-1H-imidazol-1-yl)-1,2,3,4-tetrahydro-4-quinolinyl]carbamate

Participants

Reaction Conditions

Reaction Steps

Sodium borohydride (29 mg, 0.767 mmol) was added to a solution of 1,1-dimethylethyl (3-{[4-(4-methyl-1H-imidazol-1-yl)phenyl]amino}butanoyl)carbamate (for a preparation see Intermediate 103) (340 mg, 0.949 mmol) in ethanol (6 mL) cooled at −15° C. (cold bath: ethanol/card ice). Magnesium chloride hexahydrate (202 mg, 0.996 mmol) in water (1 mL) was then slowly added keeping the temperature below 10° C.). The mixture was then stirred at 0° C. for 45 min and at room temperature for 45 min before being poured onto a stirred mixture of citric acid (456 mg, 2.371 mmol), HCl (1M in water, 10 mL) and DCM (5 mL). The resulting mixture was stirred for 30 min at room temperature then the layers were separated. The aqueous phase was basified with solid K2CO3 and extracted twice with AcOEt (25 mL). The combined organic phases were washed with water then brine, dried over MgSO4 and concentrated in vacuo. Purification of the residue by flash chromatography on silica gel (gradient: 4 to 8% MeOH in DCM) gave 1,1-dimethylethyl [(cis)-2-methyl-6-(4-methyl-1H-imidazol-1-yl)-1,2,3,4-tetrahydro-4-quinolinyl]carbamate (273 mg, 0.797 mmol, 84%) as a white solid.

Provenance & Evidence