Reaction #168003

Reaction equation

1-benzyl-4-piperidone

acetoacetamide

NaHCO3

NaHCO3

→

6-benzyl-4-methyl-5,6,7,8-tetrahydro-1,6-naphthyridin-2-ol

Solvents

Eaton's reagent

water

DCM

H2O

Conditions

Workup

1. 1
   workup.STIRRINGAfter stirring for 18 h
2. 2
   Temperaturethe reaction mixture was cooled to rt
3. 3
   workup.ADDITIONslowly poured
4. 4
   Otherthe two phases were separated
5. 5
   ExtractionThe products were extracted once with DCM (500 mL) from the aqueous layer
6. 6
   WashThe combined organic layer was washed with brine (500 mL)
7. 7
   Dryingdried over Na2SO4
8. 8
   Filtrationfiltered
9. 9
   Concentrationconcentrated under reduced pressure
10. 10
    OtherThe brown residue was triturated with acetone (200 mL)
11. 11
    OtherThe precipitated solid was collected on a funnel
12. 12
    Washwashed with acetone (100 mL)
13. 13
    Otherdried under reduced pressure

Procedure

A mixture of 1-benzyl-4-piperidone (19.6 mL, 106 mmol), acetoacetamide (11.7 g, 116 mmol) in Eaton's reagent (40 mL) was allowed to stir at 110° C. After stirring for 18 h, the reaction mixture was cooled to rt, and then slowly poured into stirred aq NaHCO3 (150 g of NaHCO3 in 1000 mL of water. The mixture was diluted with DCM (1000 mL) and H2O (50 mL), and the two phases were separated. The products were extracted once with DCM (500 mL) from the aqueous layer. The combined organic layer was washed with brine (500 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure. The brown residue was triturated with acetone (200 mL). The precipitated solid was collected on a funnel, washed with acetone (100 mL), and dried under reduced pressure to give 6-benzyl-4-methyl-5,6,7,8-tetrahydro-1,6-naphthyridin-2-ol. 1H NMR (400 MHz, CDCl3) δ ppm 12.71 (br s, 1 H), 7.26-7.35 (m, 5 H), 6.22 (s, 1 H), 3.71 (s, 2 H), 3.34 (s, 2 H), 2.70-2.73 (m, 2 H), 2.77-2.79 (m, 2 H), 2.03 (s, 3 H); MS (ESI+) m/z 255.42 (M+H)+.

Source