The general procedure for the synthesis of 3-(tert-butyl)-4-hydroxybenzonitrile from 3-(tert-butyl)-4-hydroxybenzaldehyde is as follows: with reference to the synthesis of intermediate R10 3-(1,1-dimethylethyl)-4-hydroxybenzenecarbonitrile [1399], 3-(1,1-dimethylethyl)-4-hydroxybenzaldehyde (550 mg with reference to intermediate R9) was mixed with hydroxylamine hydrochloride (322 mg , 4.63 mmol) in 8.0 mL of acetic acid under reflux conditions for 1 hour. Upon completion of the reaction, the mixture was cooled to 0 °C and subsequently poured into ether (Et2O). The mixture was washed sequentially with water and 5% aqueous sodium hydroxide solution each. The aqueous phase was extracted twice with ether (Et2O), all organic phases were combined, dried with anhydrous sodium sulfate (Na2SO4), filtered and the solvent evaporated. The residue was ground with pentane to give 540 mg of 3-tert-butyl-4-hydroxybenzonitrile. The product was characterized by 1H-NMR (400 MHz, DMSO-d6): δ 10.92 (1H, broad single peak), 7.53-7.45 (2H, multiple peaks), 6.92 (1H, double peaks), 1.34 (9H, single peak); UPLC_ipqc analysis: retention time 1.03 min, mass spectrometry detected [M-H]-peak m/z 174.
