1-Piperidinecarboxaldehyde → 5-Chloro-2-methylbenzaldehyde

Participants

Reaction Steps

To 2-bromo-4-chloro toluene (20.0 g; 97.3 mmol) in 300 mL of THF at −78° C. was added n-BuLi 2.5M (40.8 mL) dropwise. After 20 min. 1-formylpiperidine (11.4 mL; 103.0 mmol) in 10 mL of THF was added dropwise. After 30 min the reaction mixture was brought to 0° C. and quenched with HCl (10%) and diluted with EtOAc. The organic phase was collected, dry and the solvent evaporated to yield 13.3 g (89%) of 5-chloro-2-methylbenzaldehyde. This crude aldehyde was mixed with 1.1 equivalent of triethyl phosphonoacetate in THF. Sodium hydride 80% (1.3 equivalent ) was added portionwise and 1 h later the reaction was quenched with 25% NH4Cl. The reaction mixture was diluted with EtOAc and the organic phase collected, dried and the solvent removed. The crude oil was purified on a short pad of silica gel using 5% EtOAc in hexane to afford 16.67 g of the title compound.

Provenance & Evidence