Toluene → 4-Methyl-3-[(1-methylpiperidin-4-yl)oxy]aniline

Participants

Reaction Steps

Combine 4-(5-bromo-2-methyl-phenoxy)-1-methyl-piperidine (preparation 20, 3.90 g, 13.7 mmol), benzophenone imine (2.98 g, 16.44 mmol), Pd2(dba)3 (251 mg, 0.27 mmol), BINAP (512 mg, 0.82 mmol), sodium f-butoxide (1.843 g, 19.18 mmol) and toluene (40 mL) and heat at 85° C. After 9 hr., quench the reaction with saturated NaHCO3 solution, extract with ethylacetate three times, combine the organic layers, dry over Na2SO4, filter and concentrate to give a residue. Dissolve the residue in THF (55 mL) and add 5N HCl (5.5 mL) and stir. After 1 hr., dilute the mixture with 0.1N HCl, extract with ethylacetate/hexanes (1:2) twice, keep aqueous layer, adjust pH>11 with 5N NaOH, extract with methylene dichloride three time. Combine methylene dichloride layers, dry over Na2SO4, filter and concentrate to give a residue. Purify by silica gel chromatography, eluting with 6.5% 2M NH3-methanol in methylene dichloride to give the title compound as a yellow oil (2.80 g, 93%). Mass spectrum (ion spray): m/z=221.1 (M+1); 1H NMR (CDCl3, ppm): 6.79 (d, 1H), 6.09 (m, 2H), 4.16 (m, 1H), 3.41 (s, br, 1H), 2.53 (m, 2H), 2.24 (m, 2H), 2.19 (s, 3H), 2.00 (s, 3H), 1.93-1.68 (m, 4H).

Provenance & Evidence