Preparation method of RXR agonist

• Main Authors: WANG YONGDONG, HUANG ZHIPENG, HE CHUAN, ZHU SHIFA
• Format: Patent
• Language: Chinese; English
• Published: 22.11.2022
• Subjects: ACYCLIC OR CARBOCYCLIC COMPOUNDS; CHEMISTRY; METALLURGY; ORGANIC CHEMISTRY

The invention discloses a preparation method of an RXR agonist, which comprises the following steps: S1, reacting a compound as shown in a formula A with a compound as shown in a formula B under the conditions of an N-heterocyclic carbene copper catalyst, a silicon reagent for providing a hydrogen source, a solvent and organic alkali to generate a compound as shown in a formula C; s2, reacting the compound as shown in the formula C with a compound as shown in a formula D under the condition of a Loveda-Glubbs II catalyst to generate a compound as shown in a formula E; s3, removing ethyl from the compound shown in the formula E to generate an RXR agonist; wherein R is a methyl formate group, an acetyl group, a p-toluenesulfonyl group or a trifluoromethanesulfonyl group. 本发明公开了一种RXR激动剂的制备方法，包括如下步骤：S1.式A所示化合物与式B所示化合物在氮杂卡宾铜催化剂、提供氢源的硅试剂、溶剂和有机碱的条件下，反应生成式C所示化合物；S2.式C所示化合物与式D所示化合物在荷维达-格鲁布斯Ⅱ催化剂条件下反应生成式E所示化合物；S3.式E所示化合物脱除乙基，生成RXR激动剂；其中，R为甲酸甲酯基、乙酰基、对甲苯磺酰基或三氟甲磺酰基。