Water → ethyl 4-(2-methyl-7-nitro-1-oxo-2,3-dihydro-1H-isoindol-4-yl)cyclohex-3-ene-1-carboxylate

Participants

Reaction Steps

A mixture of 2-methyl-7-nitro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1H-isoindol-1-one (1.50 g, 4.72 mmol), ethyl 4-{[(trifluoromethyl)sulfonyl]oxy}cyclohex-3-ene-1-carboxylate (1.57 g, 5.19 mmol), potassium carbonate (1.95 g, 14.1 mmol) and [1,1-bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (1:1) (0.385 g, 0.472 mmol) in 1,4-dioxane (12.0 mL, 154 mmol) and H2O (3.00 mL, 166 mmol) was evacuated and refilled with Ar(g)((3×) and irradiated in the microwave at 100° C. for 30 min. The crude mixture was concentrated in vacuo to a solid and purified by CombiFlash®Rf 4X Organic Purification System [120 g RediSep® Normal-phase GOLD Silica Flash Column, dried loaded, elution gradient: 0→40% EtOAc in DCM] to afford 1.03 g (63% yield) of the desired product. 1H NMR (400 MHz, Chloroform-d) δ ppm 7.71 (d, J=8.08 Hz, 1 H), 7.45 (d, 1 H), 5.93-5.99 (m, 1 H), 4.20 (q, J=7.07 Hz, 2 H), 2.65-2.75 (m, 1 H), 2.49-2.56 (m, 2 H), 2.36-2.49 (m, 2 H), 2.16-2.24 (m, 1 H), 1.87-2.00 (m, 1 H), 1.54 (br. s., 3 H), 1.31 (t, J=7.20 Hz, 3 H). MS (ES+): m/z 346.15/347.15 (100/15) [MH+]. HPLC: tR=1.43 min (UPLC TOF, polar—3 min).

Provenance & Evidence