Diethyl Ether → 2-[1-Hydroxy-6'-(1-hydroxypentyl)-benzyl]pyridine

Participants

Reaction Conditions

Reaction Steps

To a mixture of 10 mL (85.6 mmol) of 2-bromobenzaldehyde in 300 mL of ether cooled to -45° C. was added in portions 8.56 mL (85.6 mmol) of 10M n-butyllithium in hexane over a 20 min period, and the reaction mixture was stirred at -20 for 1/2 h. To the above reaction mixture cooled to -20° C., was added 8.98 mL (88.9 mmol) of 10M n-butyl-lithium in hexane over a 10 min period, and the mixture was allowed to warm to room temperature and stirred for 1 h. The mixture was cooled to -20° C., and 12.2 mL (128 mmol) of 2-pyridinecarboxaldehyde was added rapidly and the mixture was allowed to warm to room temperature and stirred for 1 h. The above reaction mixture was poured into 150 mL of saturated ammonium chloride solution with stirring, the aqueous layer was extracted with ethyl acetate (3×200 mL), the combined organic layer was washed with brine, dried over sodium sulfate, and concentrated in vacuo to yield a brown oil. The oil was purified by chromatography on silica eluting with methylene chloride and then ether/hexane (9:1). The solvent was concentrated in vacuo, the brown oil was dissolved in methylene chloride/hexane, and removal of methylene chloride in vacuo to 1/2 of its volume afforded 19.3 g (83.2%) of 2-[1-hydroxy-6'-(1-hydroxypentyl)-benzyl]pyridine (Formula X: R1 =R7 =H; R2 =n-butyl), as a yellow solid.

Provenance & Evidence