Methyl iodide → 1-Methylpiperidine-4-carboxylic acid

A mixture of ethyl piperidine-4-carboxylate (4.72 g), methyl iodide (2.24 mL), potassium carbonate (8.29 g) and acetonitrile (50 mL) was stirred at room temperature for 2 hrs. The reaction solution was concentrated under reduced pressure, and water (150 mL) was added thereto, followed by extracting with ethyl acetate (150 mL). The ethyl acetate layer was washed with saturated brine (100 mL), and dried over anhydrous magnesium sulfate, then concentrated under reduced pressure. To the residue (2.64 g) was added 1 N aqueous solution of sodium hydroxide (20 mL), and stirred at room temperature overnight. To the reaction solution was added 1 N hydrochloric acid (20 mL) to neutralize, and concentrated under reduced pressure. To the residue was added ethanol, and the precipitate was filtered off, and the filtrate was concentrated under reduced pressure. After repeating this operation again, to the residue were added ethanol and ethyl acetate to crystallize, which gave 1-methylpiperidine-4-carboxylic acid as colorless solid (1.79 g).

1. concentrationThe reaction solution was concentrated under reduced pressure, and water (150 mL)
2. additionwas added
3. extractionby extracting with ethyl acetate (150 mL)
4. washThe ethyl acetate layer was washed with saturated brine (100 mL)
5. dry with materialdried over anhydrous magnesium sulfate
6. concentrationconcentrated under reduced pressure
7. additionTo the residue (2.64 g) was added 1 N aqueous solution of sodium hydroxide (20 mL)
8. stirringstirred at room temperature overnight
9. additionTo the reaction solution was added 1 N hydrochloric acid (20 mL)
10. concentrationconcentrated under reduced pressure
11. additionTo the residue was added ethanol
12. filtrationthe precipitate was filtered off
13. concentrationthe filtrate was concentrated under reduced pressure
14. additionto the residue were added ethanol and ethyl acetate
15. customto crystallize

ORD record

ord-a14c4f6fcc384deeb571e93149b1dfe9

Source dataset

uspto-grants-2013_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08449911B2