US 12,404,229 B2
Preparation method for trans-cyclobutane-o-dicarboxylic acid ester and derivative thereof
Hao Hong, Morrisville, NC (US); Enxuan Zhang, Tianjin (CN); Jiangping Lu, Tianjin (CN); Fuliang Wei, Tianjin (CN); Guanda Che, Tianjin (CN); and Mingjie Feng, Tianjin (CN)
Assigned to JILIN ASYMCHEM PHARMACEUTICALS CO., LTD., Jilin (CN)
Appl. No. 17/755,254
Filed by JILIN ASYMCHEM PHARMACEUTICALS CO., LTD., Jilin (CN)
PCT Filed Oct. 25, 2019, PCT No. PCT/CN2019/113428
§ 371(c)(1), (2) Date Apr. 25, 2022,
PCT Pub. No. WO2021/077424, PCT Pub. Date Apr. 29, 2021.
Prior Publication US 2022/0380292 A1, Dec. 1, 2022
Int. Cl. C07C 67/34 (2006.01)
CPC C07C 67/34 (2013.01) [C07C 2601/04 (2017.05)] 14 Claims
 
1. A preparation method for a trans-cyclobutane-o-dicarboxylic acid ester, comprising:
isomerizing a compound of formula I in an organic solvent at a temperature of 50-90° C. catalysed by an organic alkali to obtain the trans-cyclobutane-o-dicarboxylic acid ester, wherein the formula I is:

OG Complex Work Unit Chemistry
wherein:
each of R1, R2, R3 and R4 is hydrogen, and each of R5 and R6 is selected from the group consisting of alkyl of C1-C4 and benzyl;
the organic alkali is alkyl alkoxide of C1-C5;
a mole ratio of the organic alkali and the compound is 2.5:1-3.0:1; and
a volume ratio of the organic solvent and the compound is 2:1-5:1.