Morpholine → HCID 178420446, compound

Participants

Reaction Conditions

Reaction Steps

To a stirring cis-toluene-4-sulfonic acid 3-(4-pyrrolidin-1-ylmethyl-phenyl)-cyclobutylmethyl ester (example 47) (0.41 g, 1.0 mmol) in DMA (5 mL) was added an amine for example morpholine (0.18 g, 2 mmo). The reaction was then heated to 100° C. (oil bath). After 4 hr the reaction was cooled to rt and concentrated under reduced pressure. Purification of this material was accomplished by flash column chromatography, using a 45 g ISCO column, eluting with a gradient of 5%, 10%, 20%, 60% MeOH/CH2Cl2 with 0.1% NH4OH. The product containing fractions were collected and concentrated to yield the title compound (214 mg) as the TsOH salt. This material was free based by stirring in solid K2CO3 and MeOH for 2 hours. After 2 hr the methanolic solution was concentrated, diluted with CH2Cl2, filtered, and concentrated under reduced pressure to give the free base. The HCl salt was made by taken the freebase up in EtOAc and then adding a solution of HCl (2 eq, 1 M HCl, THF) to give a colorless solid.

Provenance & Evidence