Triphosgene → 1,1-Dimethylethyl 4-({[(2-bromo-6-fluoro-4-methylphenyl)amino]-carbonyl}amino)-1-piperidinecarboxylate

Participants

Reaction Conditions

Reaction Steps

2-Bromo-6-fluoro-4-methylaniline (5.2 g, 25.5 mmol) (D31) was dissolved in 1,4-dioxane (40 ml) and bis(trichloromethyl)carbonate (9.3 mmol, 2.7 g) was added at room temperature and the mixture was heated to 60° C. for 15 minutes and it was then brought up to 100° C. for a further 15 minutes. The mixture was then cooled to room temperature, filtered and the solvent was thoroughly evaporated; the crude was redissolved in dichloromethane (40 ml) and 1,1-dimethylethyl 4-amino-1-piperidinecarboxylate (2 eq., 51 mmol, ˜10.2 g) was added at room temperature very slowly. The mixture was stirred at room temperature for 1.5 hours, the solvent was then evaporated totally and the crude material was then left under vacuum for 10 minutes; dichloromethane was added again and the mixture obtained was filtered to afford the solid that is the first batch (5.2 g) of the desired product; the solvent was evaporated from the organic filtrate and the mixture obtained was re-dissolved into dichloromethane and filtered again to afford the second batch (1 g) of the desired product; the solvent was evaporated from the organic filtrate and the mixture obtained was re-dissolved into diethyl ether, filtered again, washed with methanol then with diethyl ether to afford the third batch (1.5 g) of the desired product. The three batches were combined to afford 7.7 g of the title compound, 70%, M++H=432.

Provenance & Evidence