Diisopropylethylamine → PF 04457845

To a mixture of 2-(3-piperidin-4-ylidenemethyl-phenoxy)-5-trifluoromethyl-pyridine, hydrochloride (37.1 g, 0.10 mol, see Example 1b, step 5) and phenyl pyridazin-3-ylcarbamate (21.5 g, 0.10 mol, see Example 39, steps 1 and 2) in acetonitrile (400 mL) was added dropwise diisopropylethyl amine (25.8 g, 0.20 mol). A solution formed after 2 h of stirring. The slightly turbid solution was stirred at ambient temperature for 17 h. It was poured into 2.5 L of stirred ice-water. The resulting mixture was stirred for 1 h. The solid was filtered off, rinsed with 300 mL of water and pressed dry under suction. This was dissolved in 400 mL of dichloromethane. Water was removed using a sep funnel and then the solution was dried over magnesium sulfate and concentrated in vacuo to ˜50 mL. The viscous solution was diluted with 65 mL of ethyl acetate and then with 85 mL of methyl t-butyl ether. A solution formed, and then a solid began separating. The crystallizing mixture was kept at −10° C. for 2 h and filtered. The solid was rinsed with EtOAc:MTBE (40 mL) and pressed dry under suction. Further drying in vacuo at 40° C. for 7 h provided 30.3 g (66%) of product. The mother liquor was concentrated in vacuo to 19 g of a viscous oil. This was dissolved in 15 mL of ethyl acetate. The solution was diluted with 60 mL of methyl t-butyl ether, seeded and kept at 5° C. for 18 h. The solid which crystallized was filtered off, rinsed with 10 mL of methyl t-butyl ether, and pressed dry under suction. 9.0 g (20%) of additional product was obtained. Total yield=39.3 g (86%).