Methanol → HCID 59053668, compound

Participants

Reaction Conditions

Reaction Steps

The ethyl ester Example 3-A, ethyl 2-(3-((5-cyclopropyl-3-(2-(trifluoromethoxy)phenyl)isoxazol-4-yl)methoxy)-8-azabicyclo[3.2.1]octan-8-yl)benzo[d]thiazole-6-carboxylate (20 mg, 0.033 mmol) was dissolved in THF (1.0 mL), and at RT was charged with a solution of methyl magnesium chloride (0.4 mL, 3.0 M THF, 1.2 mmol) in a dropwise fashion over a few minutes slowly enough so as not to allow the internal temperature of the reaction to exceed 30° C. After 1 hr the reaction was cooled to 0° C. and treated with MeOH (3 mL) in a dropwise fashion (rapid evolution of gas, internal temperature did not exceed 10° C.). The reaction was allowed to warm on its own accord to RT and diluted with ethyl acetate (9 mL) and the cloudy suspension was washed with 2×1 mL of 1 N HCl. The organic extracts were dried in vacuo and the resulting residue was purified using mass-directed reverse phase HPLC using gradient of 30 to 90% acetonitrile/water with 0.05% TFA as modifier. The resulting product was cold vacuum concentrated and free based using an SPE polymer support cartridge and MeOH (2 mL) mobilizing solvent (product SPE PLHCO3 MP part no PL3540-C603). All resulting methanol effluent was concentrated to furnish the title compound as a white powder.

Provenance & Evidence