Triethylamine → Methyl 1-(6-methoxy-3-(trifluoromethyl)quinolin-2-yl)piperidine-4-carboxylate

HRID 2201451Notes

Reaction equation

HRID 2201451 reaction equation
Cl[C:2]1[C:11]([C:12]([F:15])([F:14])[F:13])=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([O:16][CH3:17])[CH:8]=2)[N:3]=1.[CH3:18][O:19][C:20]([CH:22]1[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]1)=[O:21].CCN(CC)CC>CC(O)C.O>[CH3:17][O:16][C:7]1[CH:8]=[C:9]2[C:4](=[CH:5][CH:6]=1)[N:3]=[C:2]([N:25]1[CH2:26][CH2:27][CH:22]([C:20]([O:19][CH3:18])=[O:21])[CH2:23][CH2:24]1)[C:11]([C:12]([F:15])([F:14])[F:13])=[CH:10]2

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 424914Methyl isonipecotateHCID 866899362-Chloro-6-methoxy-3-(trifluoromethyl)quinoline2×

Product 1

HCID 66980108Methyl 1-(6-methoxy-3-(trifluoromethyl)quinolin-2-yl)piperidine-4-carboxylateYield 43%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 3776IsopropanolSolvent

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.

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux for 48 hours
  3. extractionextracted with DCM (100 mL×3)
  4. washthe combined organic layers were washed with brine (200 mL)
  5. dry with materialdried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customto give the crude product, which
  9. customwas purified by column chromatography on silica gel (PE/EtOAc=15/1)

Sources & evidence

ORD record
ord-b5c189901c154879b29c0723e8cf9e3a
Source dataset
uspto-grants-2016_06
Patent number
US09364481B2

Reaction notes

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