Imidazole → Tert-butyl 4-(2-(2-iodoethylthio)-5-nitrophenylamino)piperidine-1-carboxylate

Temperatur

0 °C

To a stirred solution of triphenylphosphine (1.178 g, 4.49 mmol) and imidazole (0.611 g, 8.98 mmol) in tetrahydrofuran (10 mL) at 0° C. was added iodine (1.292 g, 5.09 mmol). The resulting dark mixture was stirred at 0° C. After 5 minutes, tert-butyl 4-(2-(2-hydroxyethylthio)-5-nitrophenylamino)piperidine-1-carboxylate (1.19 g, 2.99 mmol) was added as a solution in tetrahydrofuran (5 mL). The mixture was then warmed to room temperature and stirred for 1 hour. The mixture was then diluted with ethyl acetate and washed with saturated sodium carbonate, saturated sodium thiosulfate, water, and brine. The organic phase was dried, filtered, concentrated, and then chromatographed in 1:2 ethyl acetate:hexanes, giving the desired product (1.50 g, 99%) as an orange foam. 1H NMR (DMSO-d6) δ 7.59-7.54 (m, 1H), 7.45-7.38 (m, 2H), 5.45-5.37 (m, 1H), 3.98-3.85 (m, 2H), 3.73-3.61 (m, 1H), 3.35-3.27 (m, 5H), 3.19-3.03 (m, 1H), 3.02-2.82 (m, 2H), 1.92-1.84 (m, 2H), 1.45-1.34 (m, 11H); ESI-MS (m/z, %): 530 (M+Na, 6), 452 (25), 279 (100).

1. temperatureThe mixture was then warmed to room temperature
2. stirringstirred for 1 hour
3. washwashed with saturated sodium carbonate, saturated sodium thiosulfate, water, and brine
4. customThe organic phase was dried
5. filtrationfiltered
6. concentrationconcentrated
7. customchromatographed in 1:2 ethyl acetate

ORD-Eintrag

ord-34b1376c4c794fa18236fe12c73da2c2

Quelldatensatz

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08618286B2