Citric Acid → tert-Butyl 4-((5-bromopyridin-2-yl)oxy)piperidine-1-carboxylate

Temperature

70 °C

Sodium hydride (0.20 g, 60% dispersion in mineral oil) was added to a solution of 4-hydroxypiperidine-1-carboxylic acid tert-butyl ester (0.92 g) in anhydrous 1-methyl-2-pyrrolidinone (5 ml), precooled in ice. After stirring for 30 minutes under nitrogen, 2,5-dibromopyridine (1.0 g) was added. The reaction mixture was then stirred for two hours at room temperature before heating to 70° C. for four hours. The resultant dark mixture was poured onto ice (200 ml) containing 2% citric acid (20 ml), and was extracted with diethyl ether (3×15 ml). The aqueous phase was then basified to pH 13 with solid sodium hydroxide, and extracted with diethyl ether (2×15 ml). The combined organics were washed water (3×20 ml), saturated brine (20 ml) and dried over anhydrous sodium sulfate and evaporated to give the title compound as a light brown oil (0.87 g, 58%).

1. stirringThe reaction mixture was then stirred for two hours at room temperature
2. additionThe resultant dark mixture was poured onto ice (200 ml)
3. extractionwas extracted with diethyl ether (3×15 ml)
4. extractionextracted with diethyl ether (2×15 ml)
5. washThe combined organics were washed water (3×20 ml), saturated brine (20 ml)
6. dry with materialdried over anhydrous sodium sulfate
7. customevaporated

ORD record

ord-d906daf9f0a242e19ce8fcd0939f3d6d

Source dataset

uspto-grants-2004_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06809100B2