Uses
Methyl 3-Acetyl-4-hydroxybenzoate is used to prepare and study structure-activity relationships of 2-(1-adamantyl)-4-(thio)chromenone-6-carboxylic acids as potent reversible inhibitors of human steroid sulfatase.
Synthesis
Step 2: To a degassed ethanol (3 L) solution of methyl 3-bromo-4-hydroxybenzoate (350 g, 1514.87 mmol) under nitrogen protection were sequentially added triethylamine (0.528 L, 3787.17 mmol), 1-(vinyloxy)butane (0.588 L, 4544.60 mmol), 1,1 '-bis(diphenylphosphino) ferrocene (33.1 g, 60.6 mmol) and diacetoxypalladium (8.50 g, 37.9 mmol). The reaction mixture was stirred at 70 °C overnight. After completion of the reaction, the mixture was cooled to room temperature, filtered and the filtrate was concentrated. The resulting solid was dissolved with dichloromethane (2 L), followed by the slow addition of 4 N hydrochloric acid (1.14 L, 4544 mmol) under stirring. After continued stirring for 2 h, the organic phase was separated, dried with anhydrous magnesium sulfate, filtered and concentrated to give the crude product. The crude product was dissolved in ether (5 L), stirred for 2 h, filtered, and the filtrate was concentrated to dryness to give methyl 3-acetyl-4-hydroxybenzoate (240 g, 82% yield) as a beige powder. Mass spectral data: [MH]- 193.
References
[1] Patent: US2011/98271, 2011, A1. Location in patent: Page/Page column 39
[2] Patent: WO2011/51704, 2011, A1. Location in patent: Page/Page column 99
[3] Patent: WO2012/140419, 2012, A1. Location in patent: Page/Page column 87
[4] Patent: US2012/264731, 2012, A1. Location in patent: Page/Page column 34; 35
[5] Journal of Medicinal Chemistry, 2015, vol. 58, # 2, p. 943 - 962
