3-chloro-5-methoxy-4-phenylmethoxybenzaldehyde

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirring solution of 3-chloro-4-hydroxy-5-methoxybenzaldehyde (599 mg, 3.21 mmol) in DMF (5 mL) under nitrogen was added Cs2CO3 (1.10 g, 3.38 mmol) followed by benzyl chloride (0.40 mL, 3.48 mmol) and the mixture heated at reflux for 1 h. After allowing the mixture to cool to ambient temperature the reaction was quenched by the addition of aqueous NaOH (2N, 30 mL) and the mixture concentrated under vacuum. The residue was then partitioned between NaOH (2N, 30 mL) and EtOAc (50 mL) and the layers separated. The aqueous layer was then re-extracted with EtOAc (50 mL), the layers separated and the combined organic layer washed with brine and then concentrated under vacuum. Purification by SPE (silica, 20 g cartridge) eluting with cyclohexane:EtOAc (gradient 50:1 to 10:1) afforded the title compound (632 mg). the mixture heated at reflux for 1 h was quenched by the addition of aqueous NaOH (2N, 30 mL) the mixture concentrated under vacuum The residue was then partitioned between NaOH (2N, 30 mL) and EtOAc (50 mL) the layers separated The aqueous layer was then re-extracted with EtOAc (50 mL) the layers separated the combined organic layer washed with brine concentrated under vacuum Purification by SPE (silica, 20 g cartridge) eluting with cyclohexane

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 5-Chlorovanillin (60 g., 0.32 m.), 46.8 g. of potassium carbonate (0.34 m.), 1.9 g. of sodium iodide in 1.4 l. of ethanol and 46.8 g. (0.37 m.) of benzyl chloride in 200 ml. of ethanol are reacted to give 4-benzyloxy-5-chloro-3-methoxybenzaldehyde as an orange liquid which is employed for conversion of the epoxide without purification.