2,6-Di-tert-butyl-4-methylphenol → HCID 46183920, compound

Participants

Reaction Steps

{2-[3-Bromo-4-(4-trifluoromethylpyridin-2-yloxy)-phenyl]-ethyl}-(5,8-difluoroquinazolin-4-yl)-amine (890 mg, 1.7 mmol), vinyl tri-n-butyltin (591 mg, 544 μL, 1.9 mmol), 1,4-bis(diphenylphosphino)butane (145 mg, 0.3 mmol), 2,6-di-tert-butyl-4-methylphenol (75 mg, 0.3 mmol) and Pd(OAc)2 (49 mg, 0.22 mmol) were added to a Carousel reactor tube containing toluene (5 mL) and fitted with a magnetic stir bar and a dry nitrogen gas line. The reaction mixture was heated to reflux. After 20 h, more Pd(OAc)2 (49 mg, 0.22 mmol) was added, and heating was continued. After another 20 h, the reaction was cooled. The reaction mixture was washed sequentially with water and brine, then dried (Na2SO4), filtered through a silica gel and Celite plug, and concentrated in vacuo. The residue was partitioned between acetonitrile (30 mL) and pentane (5×20 mL). The acetonitrile fraction then was purified by normal phase chromatography (silica gel with ethyl acetate/cyclohexane eluent) and reverse phase chromatography (C-18 solid phase with acetonitrile/water eluent, 0.5% H3PO4) to provide (5,8-difluoroquinazolin-4-yl)-{2-[4-(4-trifluoromethylpyridin-2-yloxy)-3-vinylphenyl]-ethyl}-amine as a white powder (375 mg), M.P. 86°. 1H NMR (CDCl3): δ 8.7 (s, 1H), 8.31 (d, 1H), 7.54 (d, 1H), 7.35 (m, 1H), 7.24 (m, 1H), 7.18 (m, 1H), 7.14 (s, 1H), 7.06 (d, 1H), 6.78 (bm, 2H), 5.76 (d, 1H), 5.26 (d, 1H), 3.97 (m, 2H), 3.07 (t, 2H). MS: m/z 472.

Provenance & Evidence