2-Iodotoluene → 2-Propyl-[4-(2-methylphenyl)-4-oxo-1-butyl]piperidine

In a 10 mL oven-dried flask was added Mg turnings (97 mg, 4.1 mmol) which were activated by the use of a heat-gun under vacuum. Under inert atmosphere was added a suspension of 2-iodotoluene (380 μl, 2.8 mmol) in Et2O (3 mL) and the reaction mixture was allowed to reflux for 1 hour. A mixture of compound 8 (0.43 g, 2.2 mmol) in CH2Cl2 (3 mL) was added via a syringe and the reaction mixture was stirred at rt overnight. The reaction mixture was quenched by addition of H2SO4 (10 mL, 2 M) and stirred at rt for 12 hours followed by addition of NaOH (10 mL, 2 M). Addition of THF (15 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), dried (MgSO4) and evaporated to dryness to produce 0.43 g of crude 9. The crude product was subjected to preparative HPLC [eluent: Buffer A: 0.1% TFA; Buffer B: 80% CH3CN+0.1%TFA] to produce an analytically pure sample of compound 9; LC-MS [M+H]+ 287 (cald. 287.2).

1. customIn a 10 mL oven-dried flask
2. temperaturea heat-gun under vacuum
3. additionUnder inert atmosphere was added
4. temperatureto reflux for 1 hour
5. additionwas added via a syringe
6. customThe reaction mixture was quenched by addition of H2SO4 (10 mL, 2 M)
7. stirringstirred at rt for 12 hours
8. additionfollowed by addition of NaOH (10 mL, 2 M)
9. additionAddition of THF (15 mL)
10. extractionwas followed by extraction with ethyl acetate (3×50 mL)
11. washthe combined organic phases are washed with brine (10 mL) and NaOH (10 mL, 2 M)
12. dry with materialdried (MgSO4)
13. customevaporated to dryness
14. customto produce 0.43 g of crude 9

ORD record

ord-2ac58bc97480436285b13dd6f0e6cd74

Source dataset

uspto-grants-2009_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07485651B2