Potassium Carbonate → 4-(2-Butynyloxy)-5-fluoro-6-(3,5-dimethylpiperidino)pyrimidine

Participants

Reaction Conditions

Reaction Steps

To a mixture obtained by adding 110.0 g of 4,5,6-trifluoropyrimidine, 114.6 g of potassium carbonate and 16.6 g of triethylamine to 220.0 g of toluene, 60.4 g of 2-butyn-1-ol was added dropwise at 25 to 30° C. over one hour, followed by stirring at 30° C. for 8 hours. Then, 220.0 g of water was added dropwise in the reaction mixture, followed by stirring for 14 hours. Then, 97.5 g of 3,5-dimethylpiperidine (a mixture of a cis-isomer and a trans-isomer in a mixing ratio of about 7:3) was added dropwise and, after the mixture was stirred at 30° C. for 6 hours, the reaction mixture was allowed to stand. After separating into the organic layer and the aqueous layer, the aqueous layer was removed and the organic layer was then washed once with 220.0 g of 5% hydrochloric acid and then washed once with 220.0 g of water. The organic layer was concentrated to obtain 213.8 g (yield: 94%) of 4-(2-butynyloxy)-5-fluoro-6-(3,5-dimethylpiperidino)pyrimidine (hereinafter referred to as the present compound (3)). Product purity 96% (HPLC)

Provenance & Evidence