Sodium hydride → HCID 86739960, compound

Participants

Reaction Conditions

Reaction Steps

A suspension of 30.3 g (0.758 mol) of 60% NaH in mineral oil in 164 ml of DMF was cooled to 3° C. and a solution of 100.0 g (0.252 mol) of diethyl 1,4-dihydro-2,6-dimethyl-4-[2-(trifluoromethyl)phenyl]3,5-pyridinedicarboxylate in 100 ml of warm DMF was added dropwise over 30 min, keeping the temperature at 15° C. or less. After the addition was complete, 75.5 g (0.406 mol) of N-(2-chloroethyl)morpholine hydrochloride was added in portions over 25 min, keeping the temperature at approximately 15° C. The cooling bath was then replaced with a heating mantle and the reaction mixture was heated at 84°-100° C.for 4.5 hrs. After cooling to 31° C. over 50 min, the reaction mixture was poured into a stirred mixture of 500 ml of H2O and 300 ml of EtOAc. When all the solids dissolved, the phases were separated and the EtOAc phase was dried over anhydrous Na2SO4 and filtered. To this stirred EtOAc solution was added a solution of 47.9 g (0.252 mol) of p-TSA H2O in 300 ml of EtOAc, giving immediate precipitation of diethyl 1,4-dihydro-2,6-dimethyl-1-[2-(4-morpholinyl)-ethyl]-4-[2-(trifluoromethyl)-phenyl]-3,5-pyridinecarboxylate p-toluenesulfonate salt. After stirring for 20 min, the product was collected, washed with EtOAc, and dried in vacuo to yield 114.5 g (67%) of diethyl 1,4-dihydro-2,6-dimethyl-1-[2-(4-morpholinyl)ethyl]-4-[2-(trifluoromethyl)-phenyl]-3,5-pyridinedicarboxylate p-toluenesulfonate salt as a white solid: mp 204°-206° C. (dec.).

Provenance & Evidence