Piperidine → Methyl 2-(4-methyl-2-(piperidin-1-yl)-6-p-tolylpyrimidin-5-yl)acetate

HRID 1399689Notes

Reaction equation

HRID 1399689 reaction equation
Cl[C:2]1[N:7]=[C:6]([CH3:8])[C:5]([CH2:9][C:10]([O:12][CH3:13])=[O:11])=[C:4]([C:14]2[CH:19]=[CH:18][C:17]([CH3:20])=[CH:16][CH:15]=2)[N:3]=1.[NH:21]1[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]1.C(N(CC)CC)C>CC1CCCO1>[CH3:8][C:6]1[C:5]([CH2:9][C:10]([O:12][CH3:13])=[O:11])=[C:4]([C:14]2[CH:19]=[CH:18][C:17]([CH3:20])=[CH:16][CH:15]=2)[N:3]=[C:2]([N:21]2[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]2)[N:7]=1

Participants

5

Reactant 3

HCID 8082PiperidineHCID 8471TriethylamineHCID 86665648Methyl 2-(2-chloro-4-methyl-6-p-tolylpyrimidin-5-yl)acetate

Product 1

HCID 66955539Methyl 2-(4-methyl-2-(piperidin-1-yl)-6-p-tolylpyrimidin-5-yl)acetateYield 53.7%

Reagents, catalysts & solvents 1

HCID 73012-MethyltetrahydrofuranSolvent

Procedure

To a solution of methyl 2-(2-chloro-4-methyl-6-p-tolylpyrimidin-5-yl)acetate (3 g; 10.32 mmol) in 2-methyltetrahydrofuran (20 ml) was added piperidine (4.09 mL; 41.3 mmol) and triethylamine (5.72 mL; 41.3 mmol). The reaction was heated under reflux for 5 h and the reaction mixture was partitioned between ethyl acetate and a saturated solution of sodium hydrogen carbonate. The phases were separated and the aqueous layer was extracted twice with ethyl acetate. The combined organic layers were dried over magnesium sulphate, filtered and concentrated under reduced pressure. Purification by flash-chromatography on silica gel using a gradient of ethyl acetate (2-20%) in heptane furnished 1.88 g (48%) of the title compound as a white solid.

Workup

  1. temperatureThe reaction was heated
  2. temperatureunder reflux for 5 h
  3. customthe reaction mixture was partitioned between ethyl acetate
  4. customThe phases were separated
  5. extractionthe aqueous layer was extracted twice with ethyl acetate
  6. dry with materialThe combined organic layers were dried over magnesium sulphate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customPurification by flash-chromatography on silica gel using a gradient of ethyl acetate (2-20%) in heptane

Sources & evidence

ORD record
ord-67de4641dc54439c8b1caf8d8e978a5c
Source dataset
uspto-grants-2014_12
Patent number
US08906906B2

Reaction notes

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