Tetrahydrofuran → tert-Butyl 3,4-dihydroxypiperidine-1-carboxylate

Temperatur

80 °C

To a stirred solution of 21 g (115 mmol) of tert-butyl 3,6-dihydropyridine-1(2H)-carboxylate from Step A in 5 mL of tetrahydrofuran was added 300 mL of water, followed by 18 g (149 mmol) of potassium chlorate. Then a solution of 200 mg of osmium tetroxide in 30 mL of water was added slowly in portions. The mixture was stirred at 80° C. for 16 h. At this time, additional portions of potassium chlorate (11.2 g, 92 mmol) and osmium tetroxide (138 mg) were added, and stirring was continued at 80° C. for another 3.5 h. The reaction mixture was partitioned between diethyl ether and water. The aqueous phase was extracted with dichloromethane and then concentrated in vacuo. The resultant residue from the aqueous phase was extracted with tetrahydrofuran. The combined organic fractions were concentrated in vacuo, and the residue was purified by flash chromatography (silica gel, 0-5% methanol/dichloromethane) to give the title compound. 1H NMR (500 MHz, CDCl3) δ 5.93 (br s, 2H), 3.92 (m, 1H)-3.83 (m, 1H), 3.63 (m, 2H), 3.39 (m, 1H), 3.25 (m, 1H), 1.84 (m, 1H), 1.72 (m, 1H), 1.47 (s, 9H). LC/MS: 240 (M+1).

1. stirringstirring
2. waitwas continued at 80° C. for another 3.5 h
3. customThe reaction mixture was partitioned between diethyl ether and water
4. extractionThe aqueous phase was extracted with dichloromethane
5. concentrationconcentrated in vacuo
6. extractionThe resultant residue from the aqueous phase was extracted with tetrahydrofuran
7. concentrationThe combined organic fractions were concentrated in vacuo
8. customthe residue was purified by flash chromatography (silica gel, 0-5% methanol/dichloromethane)

ORD-Eintrag

ord-0519e84b5b9543a68d8cf6cb537a22e7

Quelldatensatz

uspto-grants-2008_06

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07388019B2