反应详情

A solution of tert-butyl 4-hydroxypiperidine-1-carboxylate (246 g, 1.224 mol), imidazole (100 g, 1.469 mol, 1.2 eq.) and triphenylphosphine (385 g, 1.469 mol, 1.2 eq.) in THF (750 mL) was cooled using an ice bath. Then a solution of iodine (373 g, 1.469 mol, 1.2 eq.) in THF (750 mL) was added slowly over a period of 1 hour while keeping the internal temperature below 18° C. The resulting mixture was allowed to stir at room temperature for 5 hours and the mixture was diluted with ethyl acetate (2 L), brine (1 L) and water (500 mL). The organic layer was separated and the aqueous layer was extracted with ethyl acetate (1 L×2). The organic layers were combined, washed with 15% aqueous sodium sulfite (1 L), brine (1 L), dried and concentrated. The resulting residue was stirred with hexanes (2 L) and the solid was removed by filtration. The solid was stirred with hexanes (2 L×2) and filtered. The filtrate was concentrated to give 363 g of crude oil which was purified by column chromatography (eluting with hexanes/ethyl acetate=50:1 to 20:1) to afford 319 g of tert-butyl 4-iodopiperidine-1-carboxylate.

1. customthe internal temperature below 18° C
2. customThe organic layer was separated
3. extractionthe aqueous layer was extracted with ethyl acetate (1 L×2)
4. washwashed with 15% aqueous sodium sulfite (1 L), brine (1 L)
5. customdried
6. concentrationconcentrated
7. stirringThe resulting residue was stirred with hexanes (2 L)
8. customthe solid was removed by filtration
9. stirringThe solid was stirred with hexanes (2 L×2)
10. filtrationfiltered
11. concentrationThe filtrate was concentrated
12. customto give 363 g of crude oil which
13. customwas purified by column chromatography (eluting with hexanes/ethyl acetate=50:1 to 20:1)