Hydrochloric Acid → Methyl 1-(2-chloroethyl)piperidine-4-carboxylate

To a solution of 1-tert-butyl 4-methyl piperidine-1,4-dicarboxylate (5.4 g, 22.19 mmol) in ether was added hydrogen chloride (27.7 mL, 111 mmol) in dioxane. The resulted clear solution was stirred for 4 hours. Bubbles and white precipitates were observed. Then the solvent was removed and dried in vacuo. The residue was suspended in acetonitrile (50 mL), and 2-bromoethanol (1.567 mL, 22.19 mmol) was added followed by powdered K2CO3 (14.72 g, 107 mmol). After the reaction mixture was refluxed for 18 hours, it was filtered and concentrated. The residue was redissolved in water (50.0 mL) and extracted with ethyl acetate (50.0 mL). The organic layer was dried over sodium sulfate. After filtration the solvent was removed in vacuo. The residue was dissolved in DCE (50.0 mL) before sulfurous dichloride (2.428 mL, 33.3 mmol) was added. The reaction mixture was reflux for 3 hours, then all volatile was removed in vacuo, the resulting solid was suspended in ether, then filtered and washed with ether (50.0 mL), resuspended in ethyl acetate and neutralized with sodium bicarbonate. The organic layer was collected and dried with sodium sulfate to afford methyl 1-(2-chloroethyl)piperidine-4-carboxylate (1 g, 4.86 mmol, 21.91% yield) as a brown oil. 1H NMR (400 MHz, CHLOROFORM-d) δ 3.70 (s, 3H), 3.61 (t, J=7.0 Hz, 2H), 2.97-2.86 (m, 2H), 2.75 (t, J=7.2 Hz, 2H), 2.40-2.27 (m, 1H), 2.19 (m, 2H), 2.01-1.88 (m, 2H), 1.87-1.72 (m, 2H).

1. customBubbles and white precipitates
2. customThen the solvent was removed
3. customdried in vacuo
4. temperatureAfter the reaction mixture was refluxed for 18 hours
5. filtrationit was filtered
6. concentrationconcentrated
7. dissolutionThe residue was redissolved in water (50.0 mL)
8. extractionextracted with ethyl acetate (50.0 mL)
9. dry with materialThe organic layer was dried over sodium sulfate
10. filtrationAfter filtration the solvent
11. customwas removed in vacuo
12. additionwas added
13. temperatureThe reaction mixture was reflux for 3 hours
14. customall volatile was removed in vacuo
15. filtrationfiltered
16. washwashed with ether (50.0 mL)
17. customThe organic layer was collected
18. dry with materialdried with sodium sulfate

ORDレコード

ord-41f0e17ae5a141c8bc853d25dfeb3c9c

出典データセット

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08846647B2