반응 #40673

반응 방정식

KOH

19b

1-(2,2,2-trifluoroacetyl)-1′H-spiro [piperidine4,4′-quinolin]-2′(3′H)-one

triethylamine

pivaloyl chloride

HCl

→

19c

수율 79.7%

1-pivaloyl-1′H-spiro [piperidine4,4′-quinolin]-2′(3′H)-one

수율 79.7%

용매

water

water

methanol

반응 조건

후처리

1. 1
   농축concentrated
2. 2
   기타The crude reaction mixture
3. 3
   기타was evaporated from toluene
4. 4
   기타to remove water
5. 5
   workup.STIRRINGThis was stirred at rt for 4 h
6. 6
   기타to quench
7. 7
   기타the reaction
8. 8
   추출The aqueous layer was extracted with dichloromethane (3×)
9. 9
   건조the combined organics were dried (MgSO4)
10. 10
    여과filtered
11. 11
    기타evaporated
12. 12
    기타to give the crude product
13. 13
    기타The crude product was purified by flash chromatography on Biotage

실험 절차

KOH (0.65 g, 11.5 mmol) in water (3.0 mL) was added to 19b (1.20 g, 3.8 mmol) in methanol (15 mL) and stirred at rt overnight. The reaction was neutralized with conc. HCl (1 mL) and then concentrated. The crude reaction mixture was evaporated from toluene to remove water. The crude amine was taken up in dichloromethane (30 mL) and triethylamine (2.5 mL, 19.2 mmol) and pivaloyl chloride (0.9 mL, 7.7 mmol) were added. This was stirred at rt for 4 h and then water was added to quench the reaction. The aqueous layer was extracted with dichloromethane (3×) and the combined organics were dried (MgSO4), filtered and evaporated to give the crude product. The crude product was purified by flash chromatography on Biotage using EtOAc/Hexanes (50-100%) to give 19c as a white solid (0.91 g, 79%). (M+H)+=301. 1H NMR (400 MHz, CDCl3) δ ppm 7.90 (s, 1H); 7.30 (d, J=7.3 Hz, 1H); 7.22 (t, J=7.7 Hz, 1H); 7.08 (t, J=7.6 Hz, 1H); 6.78 (d, J=7.8 Hz, 1H); 4.30 (m, 2H); 3.18 (m, 2H); 2.75 (s, 2H); 1.91 (m, 2H); 1.71 (m, 2H); 1.28 (s, 9H).

출처