Reaction #84094

Reaction equation

2-chloro-6-methoxy-3-(trifluoromethyl)quinoline

Intermediate 6

2-chloro-6-methoxy-3-(trifluoromethyl)quinoline

methyl-4-piperidinecarboxylate

Et3N

→

product

Yield 43.0%

methyl 1-(6-methoxy-3-(trifluoromethyl)quinolin-2-yl)piperidine-4-carboxylate

Yield 43.0%

Solvents

IPA

water

Conditions

Workup

1. 1
   TemperatureThe mixture was heated
2. 2
   Temperatureto reflux for 48 hours
3. 3
   Extractionextracted with DCM (100 mL×3)
4. 4
   Washthe combined organic layers were washed with brine (200 mL)
5. 5
   Dryingdried over anhydrous Na2SO4
6. 6
   Filtrationfiltered
7. 7
   Concentrationconcentrated under reduced pressure
8. 8
   Otherto give the crude product, which
9. 9
   Otherwas purified by column chromatography on silica gel (PE/EtOAc=15/1)

Procedure

To a solution of 2-chloro-6-methoxy-3-(trifluoromethyl)quinoline (1.00 g, 3.85 mmol) (see Intermediate 6, Step 8 for synthesis) in IPA (5 mL) was added methyl-4-piperidinecarboxylate (5.50 g, 38.5 mmol) and Et3N (1.17 g, 11.6 mmol). The mixture was heated to reflux for 48 hours. The mixture was diluted with water (100 mL) and extracted with DCM (100 mL×3), the combined organic layers were washed with brine (200 mL), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to give the crude product, which was purified by column chromatography on silica gel (PE/EtOAc=15/1) to give the product (600 mg, yield 43%) as a solid.

Source