7765-97-1

3-(2-Hydroxypropan-2-yl)phenol is an intermediate in the preparation of DDAO (D195160).

Step 1: Synthesis of INT-04 Methyl 3-hydroxybenzoate (2.0 g, 13.3 mmol) was dissolved in THF (10 mL) under argon protection and slowly added dropwise at room temperature to a THF solution of 1 M methyl magnesium chloride (30 mL, 30.6 mmol). After the dropwise addition was completed, the reaction continued to be stirred at room temperature for 2 hours. Upon completion of the reaction, the reaction was quenched with saturated ammonium chloride solution and subsequently extracted with EtOAc (2 x 15 mL). The organic layers were combined, washed sequentially with water and brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: 20% EtOAc/hexane) to afford 3-(2-hydroxypropan-2-yl)phenol (INT-04) (1.45 g, 72.5% yield) in colorless liquid form; Rf value of 0.5 by TLC (Expanding agent: 20% EtOAc/hexane).

[1] Patent: WO2015/106164, 2015, A1. Location in patent: Page/Page column 65
[2] Patent: US2017/66791, 2017, A1. Location in patent: Paragraph 0348; 0349