Potassium Hydroxide → 1-[2-(3-Methoxy-4-nitro-phenoxy)-ethyl]-piperidine

Temperature

80 °C

1-Piperidineethanol (1.8 g, 14 mmol) was added to a mixture of powdered KOH (0.78 g, 14 mmol) and Aliquat 336 (0.56 g, 1.4 mmol), and the resulting mixture was stirred for 5 minutes at 80° C. Then 4-fluoro-2-methoxy-1-nitrobenzene (2.0 g, 12 mmol) was added, and stirring proceeded at this temperature for 30 minutes. The mixture was cooled and partitioned between methylene chloride (75 mL) and water (75 mL), and the organic phase was washed with water (75 mL) and extracted with dilute aqueous HCl (3×60 mL). The combined aqueous phases were washed with methylene chloride (3×75 mL), basified (3N NaOH), and extracted with methylene chloride (3×75 mL). The combined organic extracts were washed with water (3×100 mL), dried (MgSO4), and evaporated, providing 1.6 g, in 49% yield; 1H NMR (DMSO-d6) δ 1.48-1.53 (m, 6H), 2.40-2.44 (m, 4H), 2.67 (t, J=5.8 Hz, 2H), 3.93 (s, 3H), 4.21 (t, J=5.8 Hz, 2H), 6.67 (dd, J=9.3 Hz, J=1.5 Hz, 1H), 6.81 (d, J=1.5 Hz, 1H), 7.95 (d, J=9.3 Hz, 1H).

1. stirringstirring
2. waitproceeded at this temperature for 30 minutes
3. temperatureThe mixture was cooled
4. custompartitioned between methylene chloride (75 mL) and water (75 mL)
5. washthe organic phase was washed with water (75 mL)
6. extractionextracted with dilute aqueous HCl (3×60 mL)
7. washThe combined aqueous phases were washed with methylene chloride (3×75 mL)
8. extractionextracted with methylene chloride (3×75 mL)
9. washThe combined organic extracts were washed with water (3×100 mL)
10. dry with materialdried (MgSO4)
11. customevaporated
12. customproviding 1.6 g

ORD record

ord-26c6b5871b4f49b1b558d3c708a5ec69

Source dataset

uspto-grants-2013_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08481568B2