1,1,1-Trifluoro-2-propanol → 5-Bromo-2-methyl-3-((1,1,1-trifluoropropan-2-yl)oxy)quinoxaline

Beteiligte Stoffe

Reaktionsbedingungen

Reaktionsschritte

To a suspension of 1,1,1,-trifluoro-2-propanol (0.85 mL, 9.38 mmol) and 5-bromo-3-chloro-2-methylquinoxaline (126e) (1.21 g, 4.69 mmol) in 5 mL of THF and 3 mL of DMF at 0° C. was added NaH (60% wt. in mineral oil) (0.31 g, 7.74 mmol). The resulting dark purple homogeneous solution was stirred at 0° C. for 5 min then RT for 1 h. It was quenched with 15 mL of sat. NH4Cl aq. solution, and extracted with 2×75 mL of EtOAc. The organic extracts were concentrated and the residue was purified on a silica gel column (1-35% EtOAc in hexanes) to give 5-bromo-2-methyl-3-((1,1,1-trifluoropropan-2-yl)oxy)quinoxaline (452a) (1.39 g, 4.15 mmol, 88% yield) as an orange solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.09 (1H, m), 8.00 (1H, dd, J=8.2, 1.0 Hz), 7.60 (1H, t, J=7.9 Hz), 6.02 (1H, dt, J=13.4, 6.7 Hz), 2.62 (3H, s), 1.64 (3H, d, J=6.7 Hz). 19F NMR (376 MHz, DMSO-d6) δ ppm −77.20 (1F, s). m/z (ESI, +ve) 335.0/337.0 (M+H)+. A mixture of Pd(dppf)Cl2 (51 mg, 0.06 mmol), (BPin)2 (637 mg, 2.50 mmol), KOAc (492 mg, 5.01 mmol), 5-bromo-2-methyl-3-((1,1,1-trifluoropropan-2-yl)oxy)quinoxaline (452a) (420 mg, 1.25 mmol) in THF (5 mL) was heated in a microwave at 90° C. for 90 min. It was diluted with 50 mL of EtOAc and filtered through a pad of Celite. The filtrate was concentrated and the residue was purified on a silica gel column (25-75% EtOAc in hexanes) to give 2-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-((1,1,1-trifluoropropan-2-yl)oxy)quinoxaline (452b) (400 mg, 84% yield) as a brown solid. m/z (ESI, +ve) 383.0 (M+H)+.

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