US 12,404,245 B2
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
Lucio Claudio Rovati, Monza (IT); Roberto Artusi, Rho (IT); Filippo Magaraci, Monza (IT); and Benedetta Buzzi, Meda (IT)
Assigned to Rottapharm Biotech S.R.L., Monza (IT)
Appl. No. 17/914,063
Filed by Rottapharm Biotech S.R.L., Monza (IT)
PCT Filed Mar. 19, 2021, PCT No. PCT/EP2021/057046
§ 371(c)(1), (2) Date Sep. 23, 2022,
PCT Pub. No. WO2021/191062, PCT Pub. Date Sep. 30, 2021.
Claims priority of application No. 20166480 (EP), filed on Mar. 27, 2020.
Prior Publication US 2023/0127805 A1, Apr. 27, 2023
Int. Cl. C07D 221/20 (2006.01)
CPC C07D 221/20 (2013.01) [C07B 2200/13 (2013.01)] 15 Claims
 
1. A process for preparing (R)-6-(tert-butoxycarbonyl)-6-azaspiro[2.5]octane-5-carboxylic acid (SM1)

OG Complex Work Unit Chemistry
said process comprising the steps of:
iv) converting a compound of formula (VII) into a compound of formula (VIII)

OG Complex Work Unit Chemistry
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)

OG Complex Work Unit Chemistry
and
vi) removing bromine atoms in the presence of a reducing agent and a base in an alcoholic solvent thus obtaining (SM1)

OG Complex Work Unit Chemistry