Potassium Carbonate → 1-methyl-5-(2-oxo-1,2-dihydrospiro [3,1-benzoxazine-4,1'-cyclobutan]-6-yl)-1H-pyrrole-2-carbonitrile

Participants

Reaction Steps

To a solution of 1-methyl-1H-pyrrole-2-carbonitrile (0.84 g, 7.1 mmol) and triisopropylborate (1.8 mL, 7.8 mmol) in THF (15 mL) at 0° C. was added lithium diisopropylamide (4.6 mL, 9.2 mmol). The reaction was allowed to warm to room temperature. Upon completion by TLC, the reaction was added dropwise to a 65° C. solution of 6-bromospiro[3,1-benzoxazine-4,1′-cyclobutan]-2(1H)-one (0.38 g, 1.4 mmol), potassium carbonate (0.58 g, 4.2 mmol) dissolved in (5 mL water), and tetrakistriphenylphosphine palladium (0) (0.081 g, 0.07 mmol) in tetrahydrofuran (10 mL). Upon completion by TLC of the reaction the reaction mixture was poured into a saturated solution of ammonium chloride (100 mL), extracted with ethyl acetate (50 mL), dried with magnesium sulfate, and purified on a silica gel column (40% ethyl acetate/hexane) to give 1-methyl-5-(2-oxo-1,2-dihydrospiro[3,1-benzoxazine-4,1′-cyclobutan]-6-yl)-1H-pyrrole-2-carbonitrile (0.33 g, 79%) as a light red solid. 1H NMR (DMSO-d6): δ 10.41 (s, 1H), 7.58 (d, 1H, J=2 Hz), 7.43 (dd, 1H, J=8.2, 1.8 Hz), 7.04 (d, 1H, J=4.0 Hz), 6.39 (d, 1H, J=8.2 Hz), 6.39 (d, 1H, J=4.0 Hz), 3.73 (s, 3H), 2.55–2.49 (m, 2H), 2.05–1.90 (m, 2H), 1.88–1.83 (m, 2H). MS (ESI) m/z 294 ([M+H]+); MS (ESI) m/z 292 ([M−H]−). High resolution mass spectrometry (HRMS): calcd for C17H15N3O2, 293.1164; found (ESI_FT), 294.12311.

Provenance & Evidence