Sodium Carbonate → 5-(2,4,4-Trimethyl-1,4-dihydro-2H-3,1-benzoxazin-6-yl)thiophene-2-carbonitrile

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A mixture of 6-bromo-2,4,4-trimethyl-1,4-dihydro-2H-3,1-benzoxazine (3.6 g, 14 mmol), bis(pinacolato)diboron (5 g, 19.7 mmol), potassium acetate (4 g, 41 mmol), and [1,1′-bis(diphenylphosphino)ferrocene]palladium (II) chloride (1:1 complex with methylene chloride, 0.4 g, 0.5 mmol) in DMF (80 mL) was subject to a positive nitrogen flow to remove oxygen and then heated at 85° C. under a blanket of nitrogen for 18 hours. The mixture was allowed to cool to ambient temperature, treated with 5-bromo-2-thiophenecarbonitrile (4 g, 21 mmol), [1,1′-bis(diphenylphosphino)ferrocene]palladium (II) chloride (1:1 complex with methylene chloride, 0.4 g, 0.5 mmol), and aqueous sodium carbonate solution (2M, 35 mL, 70 mmol), and then heated at 85° C. under nitrogen for 3 hours. The reaction mixture was allowed to cool to ambient temperature, brine (100 mL) and ethyl acetate (150 mL) were added. The organic layer was separated and aqueous layer was extracted with ethyl acetate (3×50 mL). The combined organic layers were dried (MgSO4) and concentrated. The residue was purified by a flash silica gel column chromatography (THF:hexane/1:4) to afford the title compound as an off-white solid (1 g, 25%): mp 172-173° C.; 1H-NMR (DMSO-d6) δ 7.88 (d, 1H, J=4.0 Hz), 7.47 (d, 1H, J=4.0 Hz), 7.43 (d, 1H, J=2.0 Hz), 7.32 (dd, 1H, J=8.36, 2.4 Hz), 6.77 (s, 1H), 6.60 (d, 1H, J=8.4 Hz), 4.83 (m, 1H), 1.51 (s, 3H), 1.48 (s, 3H), 1.28 (d, 3H, J 5.6 Hz); MS (ESI) m/z 283 [M−H]−.

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