Di-tert-butyl dicarbonate → tert-butyl (3S)-3-hydroxypiperidine-1-carboxylate

Participants

Reaction Steps

3-Hydroxy-piperidine-1-carboxylic acid tert-butyl ester. To a mixture of sodium bicarbonate (403.3 g, 4.8 mol) and water (1.6 L) was added (S)-3-hydroxypiperidine (R)-1-(−)-camphor-10-sulfonic acid salt (3, 400.14 g, 1.2 mol) and dichloromethane (1.6 L). The mixture was stirred for 30 minutes and cooled by ice bath. To the mixture was added di-tert-butyl dicarbonate (288.1 g, 1.32 mol) portionwise in 30 minutes. The mixture was stirred at room temperature overnight. The mixture was diluted with dichloromethane (4.8 L) and H2O (4.8 L) and separated in separation funnel. The organic layer was washed with brine (2 L), dried (Na2SO4) and concentrated to give the desired product (S)-3-hydroxy-piperidine-1-carboxylic acid tert-butyl ester in quantitative yield (241.5 g).

Provenance & Evidence