5-Cyclopropylisoxazole-3-carboxylic Acid is a compound that has been used in the discovery, design and synthesis of a selective S1P3 receptor allosteric agonist (N,N-Dicyclohexyl-5-propylisoxazole-3-carboxamide).
The general procedure for the synthesis of 5-cyclopropylisoxazole-3-carboxylic acid from ethyl 5-cyclopropylisoxazole-3-carboxylate was as follows:Intermediate 16 - Preparation of 5-cyclopropylisoxazole-3-carboxylic acid. A mixture of ethyl 5-cyclopropylisoxazole-3-carboxylate (0.550 g, 3.04 mmol) with 1M aqueous sodium hydroxide (9.11 mL, 9.11 mmol) was stirred at room temperature for 72 hours. Upon completion of the reaction, the pH of the reaction solution was adjusted to 1 with 6N hydrochloric acid, followed by extraction with ethyl acetate. The organic layer was separated, dried with anhydrous magnesium sulfate and concentrated under reduced pressure to give 0.446 g of 5-cyclopropylisoxazole-3-carboxylic acid as a solid in 96% yield. The product was confirmed by mass spectrometry: ESI/APCI(+) m/z: 154 (M+H), 176 (M+Na); ESI/APCI(-) m/z: 152 (M-H).
[1] Journal of Medicinal Chemistry, 2016, vol. 59, # 1, p. 358 - 373
[2] Patent: WO2010/142801, 2010, A1. Location in patent: Page/Page column 151
[3] Patent: US2003/236287, 2003, A1. Location in patent: Page 46, 47
[4] Patent: WO2016/40502, 2016, A1. Location in patent: Page/Page column 65
[5] Patent: WO2016/40504, 2016, A1. Location in patent: Paragraph 0194
