Reaction #40673

Reaction equation

KOH

19b

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

triethylamine

pivaloyl chloride

HCl

→

19c

Yield 79.7%

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

Yield 79.7%

Solvents

water

water

methanol

Conditions

Workup

1. 1
   Concentrationconcentrated
2. 2
   OtherThe crude reaction mixture
3. 3
   Otherwas evaporated from toluene
4. 4
   Otherto remove water
5. 5
   workup.STIRRINGThis was stirred at rt for 4 h
6. 6
   Otherto quench
7. 7
   Otherthe reaction
8. 8
   ExtractionThe aqueous layer was extracted with dichloromethane (3×)
9. 9
   Dryingthe combined organics were dried (MgSO4)
10. 10
    Filtrationfiltered
11. 11
    Otherevaporated
12. 12
    Otherto give the crude product
13. 13
    OtherThe crude product was purified by flash chromatography on Biotage

Procedure

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).

Source