Patent ID: 11873305
Assignee: HOFFMANN-LA ROCHE, INC.
Field: Organic fine chemistry (Chemistry)
Classification: CPC C | IPC C

Claim 0:
1. A process for the preparation of a compound of formula (II):, or a stereoisomer thereof,
wherein:
each R1a is independently hydrogen, halogen, unsubstituted C1-3 alkyl, unsubstituted C1-3 haloalkyl, or unsubstituted C1-3 alkoxy;
each R1b is independently hydrogen, halogen, unsubstituted C1-3 alkyl, unsubstituted C1-3 haloalkyl, or unsubstituted C1-3 alkoxy;
each R2 is independently halogen, cyano, unsubstituted C1-3 alkyl, unsubstituted C1-3 haloalkyl, hydroxyl, or unsubstituted C1-3 alkoxy;
m is 0, 1, or 2; and
n is 1, 2, or 3;

wherein the process comprises the following steps:
(a) contacting a compound of formula (III):, or a salt or stereoisomer thereof,
wherein:
each R2 is independently halogen, cyano, unsubstituted C1-3 alkyl, unsubstituted C1-3 haloalkyl, hydroxyl, or unsubstituted C1-3 alkoxy; and
m is 0, 1, or 2;

with a sulfonic acid selected from the group consisting of H2SO4 and ClSO3H, to form a compound of formula (IIIa):, or a salt or stereoisomer thereof,
wherein:
each R2 is independently halogen, cyano, unsubstituted C1-3 alkyl, unsubstituted C1-3 haloalkyl, hydroxyl, or unsubstituted C1-3 alkoxy; and
m is 0, 1, or 2;

(b) contacting the compound of formula (Ma) of step (a), or a salt or stereoisomer thereof, with a base, to form a compound of formula (IV):, or a salt or stereoisomer thereof,
wherein:
each R2 is independently halogen, cyano, unsubstituted C1-3 alkyl, unsubstituted C1-3 haloalkyl, hydroxyl, or unsubstituted C1-3 alkoxy; and
m is 0, 1, or 2;

(c) hydrogenating the compound of formula (IV) of step (b), or a salt or stereoisomer thereof, in the presence of a catalyst, to form a compound of formula (V):, or a salt or stereoisomer thereof,
wherein:
each R2 is independently halogen, cyano, unsubstituted C1-3 alkyl, unsubstituted C1-3 haloalkyl, hydroxyl, or unsubstituted C1-3 alkoxy; and
m is 0, 1, or 2; and

(d) contacting the compound of formula (V) of step (c), or a salt or stereoisomer thereof, with a compound of formula (VI):, or a stereoisomer thereof,
wherein:
each R1a is independently hydrogen, halogen, unsubstituted C1-3 alkyl, unsubstituted C1-3 haloalkyl, or unsubstituted C1-3 alkoxy;
each R1b is independently hydrogen, halogen, unsubstituted C1-3 alkyl, unsubstituted C1-3 haloalkyl, or unsubstituted C1-3 alkoxy; and
n is 1, 2, or 3;

thereby forming the compound of formula (II) above, or a stereoisomer thereof.