US 11,987,548 B2
Methods of making bempedoic acid and compositions of the same
Richard Copp, Pinckney, MI (US); Mohamed Abdelnasser, New City, NY (US); Christopher M. Cimarusti, Clementon, NJ (US); Jonathan Lane, Longmont, CO (US); Michael Barkman, Louisville, CO (US); Rasidul Amin, Cary, NC (US); Arthur John Cooper, Mentor, OH (US); Damodaragounder Gopal, Highland Heights, OH (US); and Philipp Selig, Linz (AT)
Assigned to Esperion Therapeutics, Inc., Ann Arbor, MI (US)
Filed by Esperion Therapeutics, Inc., Ann Arbor, MI (US)
Filed on Jul. 19, 2022, as Appl. No. 17/867,744.
Application 17/867,744 is a continuation of application No. 17/150,325, filed on Jan. 15, 2021, granted, now 11,407,705.
Application 17/150,325 is a continuation of application No. PCT/US2020/038622, filed on Jun. 19, 2020.
Claims priority of provisional application 62/864,873, filed on Jun. 21, 2019.
Prior Publication US 2023/0183160 A1, Jun. 15, 2023
This patent is subject to a terminal disclaimer.
Int. Cl. C07C 51/04 (2006.01); C07C 59/285 (2006.01)
CPC C07C 51/04 (2013.01) [C07C 59/285 (2013.01); C07B 2200/13 (2013.01)] 20 Claims
 
1. A method of preparing a pharmaceutical material comprising a compound of formula (V):

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the method comprising:
(a) contacting ethyl isobutyrate with a substituted 5-chloropentane in the presence of a first base to form a compound of formula (I):

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wherein the substituted 5-chloropentane is selected from the group consisting of 1-bromo-5-chloropentane and 1-iodo-5-chloropentane;
(b) contacting the compound of formula (I) with a salt of formula [M]+[X]−to form a compound of formula (II):

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wherein [M]+ is selected from the group consisting of Li+, Na+ and K+, and [X]− is I−;
(c) contacting the compound of formula (II) with toluenesulfonylmethyl isocyanide in the presence of a second base to form a first intermediate, and contacting the first intermediate with an acid to form a compound of formula (IV):

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and
(d) contacting the compound of formula (IV) with a reducing agent to form a second intermediate, and contacting the second intermediate with a hydrolyzing base to form a compound of formula (V),
wherein the pharmaceutical material comprises 0.0001% to less than or equal to 0.15% of the compound of formula (VI):

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based on the total weight of the pharmaceutical material.