Isopropanol → 3-Bromo-5-(propan-2-yloxy)pyridine

A slurry of 5-amino-3-bromopyridine (1.29 g, 7.46 mmol) in 6M HCl solution (5 mL) was stirred 30 min at ambient temperature. The mixture was concentrated under high vacuum, and the residue was vacuum dried for 15 h at 50° C., affording a tan solid. The solid was slurried in 2-propanol (25 mL), and treated with isoamyl nitrite (1.70 g, 15.00 mmol). The mixture was stirred and heated under reflux for 1.5 h. The solution was concentrated by rotary evaporation, and the residue was partitioned between diethyl ether and 1M NaOH solution. The aqueous layer was separated and extracted with ether. The combined ether extracts were dried (Na2SO4), filtered and concentrated by rotary evaporation producing an orange oil (2.03 g). The oil was purified by vacuum distillation, collecting the fraction with bp 105–115° C. at 9 mm Hg. The distilled product was further purified by column chromatography on silica gel, eluting with 10→20% (v/v) diethyl ether in hexane. Selected fractions, based upon TLC analysis (Rf 0.40 in hexane-ether, (4:1, v/v)) were combined and concentrated by rotary evaporation to give 566.0 mg (35.2%) of a clear, colorless oil.

1. concentrationThe mixture was concentrated under high vacuum
2. customdried for 15 h at 50° C.
3. customaffording a tan solid
4. temperatureheated
5. temperatureunder reflux for 1.5 h
6. concentrationThe solution was concentrated by rotary evaporation
7. customthe residue was partitioned between diethyl ether and 1M NaOH solution
8. customThe aqueous layer was separated
9. extractionextracted with ether
10. dry with materialThe combined ether extracts were dried (Na2SO4)
11. filtrationfiltered
12. concentrationconcentrated by rotary evaporation

ORD record

ord-44cc3ce46e1a4447ab569dc8aafce1d1

Source dataset

uspto-grants-2006_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07060826B2