반응 #60656

반응 방정식

4-Bromo-4′-fluorobiphenyl

N-tert-butoxycarbonyl piperazine

sodium tert-butoxide

toluene

→

tert-butyl 4-(4′-fluoro[1,1′-biphenyl]-4-yl)-1-piperazinecarboxylate

수율 88.0%

용매

ether

반응 조건

후처리

1. 1
   여과The warm mixture was filtered
2. 2
   세척the solids were washed twice with warm toluene
3. 3
   농축the filtrate was concentrated in vacuo
4. 4
   기타giving an orange-red crude, which
5. 5
   여과The solid was filtered off
6. 6
   세척washed with small volumes of ether
7. 7
   기타dried in vacuo at 45° C. over night

실험 절차

4-Bromo-4′-fluorobiphenyl (4.46 g, 17.8 mmol), N-tert-butoxycarbonyl piperazine (3.97 g, 21.3 mmol), sodium tert-butoxide (2.39 g, 24.9 mmol), racemic 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (rac-BINAP) (0.082 g, 0.131 mmol), bis-(dibenzylideneacetone)palladium(0) (0.041 g, 0.045 mmol) and dry toluene (45 mL) were stirred at 80° C. under nitrogen atmosphere for six hours. The warm mixture was filtered, the solids were washed twice with warm toluene and the filtrate was concentrated in vacuo giving an orange-red crude, which was stirred with ether (50 mL) for two hours. The solid was filtered off, washed with small volumes of ether and dried in vacuo at 45° C. over night to give 5.57 g (88% yield) of tert-butyl 4-(4′-fluoro[1,1′-biphenyl]-4-yl)-1-piperazinecarboxylate. This product (5.52 g, 15.5 mmol) was dissolved in dioxane (150 mL) and stirred with 4M hydrochloric acid (8.1 mL) at RT over night. Concentrated hydrochloric acid (3.0 mL) was added and stirring was continued at 45° C. for 1.5 hours and at 60° C. for 1 hour. The solution was concentrated to dryness and the solid was triturated with ether (100 mL), filtered, washed with small volumes of ether and dried in vacuo at 45° C. for two hours to give 5.26 g (103% yield) of 1-(4′-fluoro[1,1′-biphenyl]-4-yl)piperazine dihydrochloride as a light-yellow salt.

출처