2-(4-Fluorophenyl)ethyl 4-methylbenzenesulfonate → (S)-N-(1-(2-(4-fluorophenyl)ethyl)pyrrolidin-3-yl)-1-adamantanecarboxamide

Participants

Reaction Steps

(S)-N-(Pyrrolidin-3-yl)-1-adamantanecarboxamide (48 g) and 2-(4-fluorophenyl)ethyl p-toluenesulfonate (38 g) were reacted under the same conditions as in Example 1 to give (S)-N-(1-(2-(4-fluorophenyl)ethyl)pyrrolidin-3-yl)-1-adamantanecarboxamide (65 g), melting point 114-116° C. The obtained free basic compound (65 g) was dissolved in ethyl acetate, and 20% hydrochloric acid-isopropanol solution (35 g) was added thereto. After cooling, the precipitated crystals were collected by filtration to yield 57.4 g of crystals. The filtrate was concentrated under reduced pressure, ethyl acetate was added to the obtained residue. After cooling, the precipitated crystals were collected by filtration to yield 10.9 g of crystals. The obtained crystals were combined and recrystallized from a mixed solvent of ethanol (400 mL) and water (1500 mL) using activated carbon to give (S)-N-(1-(2-(4-fluorophenyl)ethyl)pyrrolidin-3-yl)-1-adamantanecarboxamide hydrochloride monohydrate (54 g), melting point 201-204° C.

Provenance & Evidence