The general procedure for the synthesis of trans-methyl-4-(hydroxymethyl)cyclohexanecarboxylic acid from methyl trans-4-(hydroxymethyl)cyclohexanecarboxylate was as follows: oxalyl chloride (7.74 g, 61.0 mmol) was slowly added to an anhydrous dichloromethane (400 mL) solution of dimethyl sulfoxide (9.53 g, 122 mmol) at -78 °C. After removing the cooling bath, the reaction mixture was stirred at -50 °C for 5 min. Subsequently, a solution of methyl trans-4-hydroxymethyl-cyclohexanecarboxylate (8.75 g, 50.8 mmol) in dichloromethane (108 mL) was added at -65 °C. After continued stirring for 30 minutes, triethylamine (25.7 g, 254 mmol) was added. Fifteen minutes after the addition was complete, the cooling bath was removed. The reaction mixture was quenched with 1 M aqueous hydrochloric acid (152 mL, 152 mmol) at -10 °C. The organic and aqueous layers were separated, and the organic layer was washed sequentially with two parts of 250 mL of water and one part of 100 mL of brine, and then dried with anhydrous sodium sulfate. Finally, a yellow oily trans-methyl-4-formylcyclohexanecarboxylic acid (9.3 g, quantitative yield) was obtained by vacuum concentration, which could be used directly in the next reaction without further purification.MS m/e: 170 (M+).
