Potassium Hydroxide → Ethyl 3-methyl-4-(methylamino)-1-piperidinecarboxylate

Temperature

0 °C

Methylamine hydrochloride (10 g, 148 mmol) was added to the stirred solution of 1-carbethoxy-3-methyl-4-piperidone (7 g, 37.83 mmol) obtained as described in Preparation 1, in methanol (50 ml) followed by 8.3 g (148 mmol) KOH. Stirring was continued for 3 hr at ambient temperature. The resulting mixture was cooled at 0° C. and sodium cyanoborohydride (3.0 g, 46.0 mmol) was added to it. Cooling was removed after 10 min. and resulting mixture was stirred for 12 hr at ambient temperature. The reaction mixture was concentrated to dryness, triturated with water, acidified with conc. HCl (pH 3˜4) and extracted with ethyl acetate to remove impurities. The aqueous layer was basified with 1 M sodium hydroxide solution (pH˜10) and extracted with ethyl acetate. Ethyl acetate extract was dried (Na2SO4) and concentrated to dryness to give 1-carbethoxy-4-methylamino-3-methylpiperidine. Yield 4.0 g (50%), C10H20N2O2, m/z 201 (M+1), PMR (CDCl3): 0.92 (dd, 3H), 1.26 (t, 3H), 1.54 (m, 1H), 2.1 (m, 2H), 2.34 (s, 3H), 2.62 (m, 1H) 2.86 (m, 1H), 3.06 (m, 1H), 3.46 (m, 1H), 3.72 (m, 1H), 4.1 (q, 2H).

1. customobtained
2. temperatureCooling
3. customwas removed after 10 min.
4. customresulting mixture
5. stirringwas stirred for 12 hr at ambient temperature
6. concentrationThe reaction mixture was concentrated to dryness
7. customtriturated with water
8. extractionextracted with ethyl acetate
9. customto remove impurities
10. extractionextracted with ethyl acetate
11. extractionEthyl acetate extract
12. dry with materialwas dried (Na2SO4)
13. concentrationconcentrated to dryness

ORD record

ord-78f3497e4663442e97928a370df259f2

Source dataset

uspto-grants-2005_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06964966B2