Methanesulfonyl chloride → 3-(1-Azidoethyl)-1-(benzyloxycarbonyl)piperidine

Temperatur

0 °C

To a solution of 1-(benzyloxycarbonyl)-3-(1-hydroxyethyl)piperidine (510 mg, 1.94 mmol) in methylene chloride (5 mL) at 0° C. was added diisopropylethylamine (507 μL, 2.91 mmol) followed by methanesulfonyl chloride (180 μL, 2.33 mmol). After stirring 10 min at 0° C., the ice bath was removed and the mixture stirred at room temperature for 30 min The reaction mixture was diluted with EtOAc then was washed with saturated aqueous NaHCO3, 1N HCl, saturated aqueous NaHCO3 and brine, respectively. The organic extract was dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude material was dissolved in DMF (5 mL), and to this was added sodium azide (190 mg, 2.91 mmol). The mixture was heated at 100° C. for 2 h. After cooling to room temperature, the reaction mixture was diluted with EtOAc and washed with H2O (3×20 mL) followed by brine. The organic layer was dried over Na2SO4. The crude material was purified by flash chromatography using 1:15 EtOAc:hexane system to obtain 442 mg of the title compound. Partial 1H NMR (500 MHz, CDCl3): δ 7.34 (m, 5H); 5.12 (br s, 2H); 3.38 (m, 1H); 1.3 (br s, 3H). Mass spectrum 289.4 (ESI, M+1).

1. customthe ice bath was removed
2. stirringthe mixture stirred at room temperature for 30 min The reaction mixture
3. additionwas diluted with EtOAc
4. washthen was washed with saturated aqueous NaHCO3, 1N HCl, saturated aqueous NaHCO3 and brine
5. extractionThe organic extract
6. dry with materialwas dried over Na2SO4
7. filtrationfiltered
8. concentrationconcentrated under reduced pressure
9. dissolutionThe crude material was dissolved in DMF (5 mL)
10. temperatureThe mixture was heated at 100° C. for 2 h
11. temperatureAfter cooling to room temperature
12. washwashed with H2O (3×20 mL)
13. dry with materialThe organic layer was dried over Na2SO4
14. customThe crude material was purified by flash chromatography

ORD-Eintrag

ord-9568ed399f3c462f8b63ceae40ba4ac1

Quelldatensatz

uspto-grants-2001_12

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US06329380B1