4-Iodo-m-xylene → 4-n-Butyl-1-[4-(2,4-dimethylphenyl)-4-oxo-1-butyl]piperidine

In a 10 mL oven-dried flask charged with Mg turnings (95 mg, 3.9 mmol) which was activated under vacuum by the use of a heat-gun. Under inert atmosphere was added a suspension of 1-iodo-2,4-dimethylbenzene (0.69 g, 2.9 mmol) in Et2O (4.5 mL) under spontaneously reflux, and the reaction mixture was allowed to reflux for 3 hours. Compound 4 (0.41 g, 2.0 mmol) dissolved in CH2Cl2 (2 mL) was added under inert atmosphere to the reaction mixture and left stirring at rt overnight. The reaction mixture was quenched by addition of H2SO4 (8 mL, 2 M) and stirred at rt for 4 hours, then the reaction mixture was basified by addition of NaOH (20 mL, 2 M). Addition of THF (20 mL) was followed by extraction with ethyl acetate (3×50 mL) and the combined organic phases are washed with brine (10 mL) and NaOH (10 mL, 2 M), and the organic phases were dried (MgSO4) and evaporated to dryness to produce 0.61 g of crude 20. The crude product was subjected to CC [eluent: CH2Cl2:MeOH (99:1)] to give pure 20 (0.21 g, 35%); LC-MS [M+H]+ 315 (cald. 315.5).

1. customIn a 10 mL oven-dried flask
2. additionUnder inert atmosphere was added
3. temperatureunder spontaneously reflux
4. temperatureto reflux for 3 hours
5. additionwas added under inert atmosphere to the reaction mixture
6. waitleft
7. customThe reaction mixture was quenched by addition of H2SO4 (8 mL, 2 M)
8. stirringstirred at rt for 4 hours
9. additionthe reaction mixture was basified by addition of NaOH (20 mL, 2 M)
10. additionAddition of THF (20 mL)
11. extractionwas followed by extraction with ethyl acetate (3×50 mL)
12. washthe combined organic phases are washed with brine (10 mL) and NaOH (10 mL, 2 M)
13. dry with materialthe organic phases were dried (MgSO4)
14. customevaporated to dryness
15. customto produce 0.61 g of crude 20

ORD record

ord-6a485b0e065241e48cc92bc9c3d208a5

Source dataset

uspto-grants-2003_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06528529B1