반응 #1975586

반응 방정식

water

1,3-dibromo-5-fluorobenzene

sodium hydride

4-hydroxy-1-methylpiperidine

→

title compound

수율 54.0%

4-(3,5-Dibromophenoxy)-1-methylpiperidine

수율 54.0%

용매

DMF

DMF

DMF

반응 조건

후처리

1. 1
   workup.STIRRINGthe reaction mixture was stirred at 65° C. for 3 days
2. 2
   추출extracted with ethyl acetate (150 mL)
3. 3
   세척The organic layer was washed with water (100 mL)
4. 4
   세척was then washed with acetonitrile
5. 5
   세척eluted with 2N ammonia in methanol

실험 절차

To a suspension of sodium hydride (60% in mineral oil, 600 mg, 15.0 mmol) in DMF (20 mL), at 65° C., was slowly added a solution of 4-hydroxy-1-methylpiperidine (1.15 g, 10 mmol) in DMF (7.0 mL). After stirring for 1 h, a solution of 1,3-dibromo-5-fluorobenzene (1.26 mL, 10.0 mmol) in DMF (7.0 mL) was added and the reaction mixture was stirred at 65° C. for 3 days. The mixture was allowed to cool to ambient temperature then poured into water (100 mL) and extracted with ethyl acetate (150 mL). The organic layer was washed with water (100 mL) and loaded onto an SCX-2 cartridge, which was then washed with acetonitrile and eluted with 2N ammonia in methanol. Concentration of the basic methanolic fraction in vacuo gave the title compound (1.88 g, 54%). 1H NMR (CDCl3, 400 MHz): 7.22 (t, J=1.6 Hz, 1H), 6.98 (d, J=1.7 Hz, 2H), 4.31-4.23 (m, 1H), 2.69-2.59 (m, 2H), 2.37-2.18 (m, 5H), 2.01-1.92 (m, 2H), 1.86-1.75 (m, 2H). LCMS (Method B): RT=2.3 min, M+H+=350.

출처