The general procedure for the synthesis of 4-(hydroxymethyl)piperidine-1-carbaldehyde from 4-(hydroxymethyl)piperidine and methyl formate was as follows: 4-(hydroxymethyl)piperidine (10 g, 87 mmol) was dissolved in methyl formate (7 mL, 113 mmol) at 0 °C and the reaction was maintained at this temperature for 30 min. The reaction system was then warmed to 20 °C and stirring was continued for 90 min. Solid sodium hydroxide pellets (0.87 g) were added to the reaction mixture and the mixture was allowed to stand overnight. Upon completion of the reaction, it was diluted with the addition of dichloromethane and the solid sodium hydroxide was removed by filtration. The filtrate was treated with an ether solution (10 mL) of 1 M hydrochloric acid and subsequently filtered through diatomaceous earth. Finally, the solvent was removed by distillation under reduced pressure to give the crude product 4-(hydroxymethyl)piperidine-1-carbaldehyde. The product was characterized by 1H NMR (400 MHz, CDCl3) with the following chemical shifts: 0.85-1.1 (2H, m); 1.55-1.85 (3H, m); 2.5-2.7 (1H, m); 2.95-3.1 (1H, m); 3.3 (2H, d, J=7 Hz); 3.6-3.7 (1H, m); 4.1-4.3 ( 1H, m); 8 (1H, s).
