ethyl 3-(cyclobutylamino)-2,2-difluoropropanoate

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 17.76 g (0.086 mole) 3-cyclobutylamino-2,2-difluoropropionic acid ethyl ester in 10 mL of ethyl acetate was added dropwise to a mixture of 16.6 g (0.086 mole) of 2,4-dichloro-5-nitro-pyrimidine, 28.9 g (0.344 mole) of sodium bicarbonate and 100 mL of ethyl acetate at 0 degrees. The cooling bath was removed and the reaction was stirred at room temperature for 18 h. Activated charcoal was added, and the mixture was filtered through a pad of Celite, washing the filter pad with ethyl acetate. The filtrate was concentrated under reduced pressure and the residue purified by silica gel chromatography (elution with hexanes-ethyl acetate, gradient 100:0-50:50), to give 11.6 g of 3-[(2-chloro-5-nitro-pyrimidin-4-yl)-cyclobutyl-amino]-2,2-difluoro-prop ionic acid ethyl ester (IV-1). The cooling bath was removed Activated charcoal was added the mixture was filtered through a pad of Celite washing the filter pad with ethyl acetate The filtrate was concentrated under reduced pressure the residue purified by silica gel chromatography (elution with hexanes-ethyl acetate, gradient 100:0-50:50)