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

Temperature

-45 °C

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.

1. temperatureTo the above reaction mixture cooled to -20° C.
2. temperatureto warm to room temperature
3. stirringstirred for 1 h
4. temperatureThe mixture was cooled to -20° C.
5. temperatureto warm to room temperature
6. stirringstirred for 1 h
7. customThe above reaction mixture
8. stirringwith stirring
9. extractionthe aqueous layer was extracted with ethyl acetate (3×200 mL)
10. washthe combined organic layer was washed with brine
11. dry with materialdried over sodium sulfate
12. concentrationconcentrated in vacuo
13. customto yield a brown oil
14. customThe oil was purified by chromatography on silica eluting with methylene chloride
15. concentrationThe solvent was concentrated in vacuo
16. dissolutionthe brown oil was dissolved in methylene chloride/hexane
17. customremoval of methylene chloride in vacuo to 1/2 of its volume

ORD record

ord-39922551f964476b9585dc84ae50cf37

Source dataset

uspto-grants-1996_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05554620