Sodium hydride → 3,8-Dimethyl-1-oxo-2-phenyl-1,2-dihydro-isoquinoline-4-carboxylic acid ethyl ester

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Reaction Steps

To a cold (ice/water bath) solution of 2-bromo-6-methyl-benzoic acid (650 mg, 3.023 mmol) and 3-phenylamino-but-2-enoic acid ethyl ester (750 mg, 3.65 mmol) in acetonitrile (10 ml), sodium hydride (267 mg, 6.67 mmol, 60% dispersion in mineral oil) was added in portions. The cold bath was removed and the mixture was sonicated at ambient temperature until gas evolution ceased (10 min). Copper (I) bromide was added (957 mg, 6.67 mmol) and the obtained suspension was flushed with argon, sealed and heated under microwave irradiation at +80° C. for 30 min. LC-MS indicated a full conversion to 2-(1-ethoxycarbonyl-2-phenylamino-propenyl)-6-methyl-benzoic acid (LC-MS (m/z) 340.4 (MH+); tR=1.59. The obtained suspension was heated at +160° C. under microwave irradiation for 30 min. It was diluted with ethyl acetate (50 ml) and filtered. The obtained organic solution was washed with 1M HCl (3×50 ml), water (2×10 ml) and sat. aq. NaHCO3 solution (30 ml), absorbed on SiO2 (3 g) and flash chromatographed on SiO2 (50 g, gradient heptane-30% ethyl acetate in heptane) to give 217 mg of yellow oil. Yield 22%. LC-MS (m/z) 322.2 (MH+); tR=1.62. 1H NMR (500 MHz, DMSO-d6): 1.32 (t, 3H), 1.91 (s, 3H), 2.74 (s, 3H), 4.39 (q, 2H), 7.3 (d, 1H), 7.36 (overlapping m, 3H), 7.49 (m, 1H), 7.55 (t, 2H), 7.61 (t, 1H).

Provenance & Evidence