반응 #61067

반응 방정식

Et3N

4-methoxy-2-methylaniline

KOt-Bu

4-chlorobutyryl chloride

→

title compound

수율 92.0%

1-(4-Methoxy-2-methylphenyl)pyrrolidin-2-one

수율 92.0%

용매

THF

Water

THF

THF

반응 조건

후처리

1. 1
   온도The internal temperature was maintained at circa 10° C.
2. 2
   기타the internal temperature <10° C
3. 3
   workup.STIRRINGThe reaction mixture was stirred at that temperature for 30 min
4. 4
   기타the phases were separated
5. 5
   workup.ADDITIONThe organic layer was treated with conc. HCl (250 mL) and water (1.26 L)
6. 6
   기타the phases were separated
7. 7
   추출The combined aqueous layers were extracted with EtOAc (2.6 L)
8. 8
   세척the combined organic layers were washed with brine (2 L)
9. 9
   기타The solvent was evaporated
10. 10
    기타the residue purified by flash chromatography (Biotage 150, EtOAc/cHex 8:2)

실험 절차

To a solution of Et3N (156 mL, 1 eq) and 4-methoxy-2-methylaniline (150 g, 1.09 mole) in anh. THF (2.4 L), in a 10 L reaction vessel, at 0° C., under N2, was added dropwise a solution of 4-chlorobutyryl chloride (126 mL, 1 eq) in anh. THF (480 mL). The internal temperature was maintained at circa 10° C. and the reaction mixture was stirred for 1.5 hr. It was cooled down to 0° C. and KOt-Bu 1M/THF (2.64 L, 2.4 eq) was added dropwise over a period of 1.5 hr, keeping the internal temperature <10° C. The reaction mixture was stirred at that temperature for 30 min. Water (1.5 L) was then added slowly (20 min) and the phases were separated. The organic layer was treated with conc. HCl (250 mL) and water (1.26 L) and the phases were separated. The combined aqueous layers were extracted with EtOAc (2.6 L) and the combined organic layers were washed with brine (2 L). The solvent was evaporated and the residue purified by flash chromatography (Biotage 150, EtOAc/cHex 8:2) to give the title compound as a pale brown solid (206 g, 92%).

출처