Process for the preparation of (R)-4-(1-(6-(4-(trifluoromethyl)benzyl)-6-azaspiro(2.5)octane-5-carboxamido)-cyclopropyl) benzoic acid or a salt thereof

• Main Authors: MAGARACI, Filippo, ROVATI, Lucio Claudio, ARTUSI, Roberto, BUZZI, Benedetta
• Format: Patent
• Language: English
• Published: 27.10.2022
• Subjects: CHEMISTRY; HETEROCYCLIC COMPOUNDS; METALLURGY; ORGANIC CHEMISTRY

The present invention provides a process for preparing (R)-6-(tert-butoxycarbonyl)-6- azaspiro[2.5]octane-5-carboxylic acid (SM1), said process comprising the step of: iv) converting a compound of formula (VII) into a compound of formula (VIII) using a Wittig reagent in a suitable solvent; v) reacting through the Makosza reaction the compound of Formula (VIII) using bromoform and a suitable base to obtain cyclopropane compound of Formula (IX); and vi) removing bromine atoms in the presence of a reducing agent and a base in an alcoholic solvent thus obtaining (SM1). The invention relates also to a process for the conversion of the compound (SM1) for preparing (R)- 4-(1-(6-(4-(trifluoromethyl)benzyl)-6-azaspiro[2.5]octane-5-carboxamido)cyclopropyl) benzoic acid (IV) or a salt thereof. The salt is preferably the sodium salt, more preferably the polymorphic form A of sodium (R)-4-(1-(6-(4-(trifluoromethyl)benzyl)-6- azaspiro[2.5]octane-5-carboxamido)-cyclopropyl) benzoate characterized by a powder XRD spectrum with peaks at values of the angle 2θ ±0.2° of 4.3, 5.0, 5.8, 6.4, 7.1, 8.3, 8.7, 12.8, 15.3, 15.9.