Tosylmethyl isocyanide → ethyl 4-(4-nitrophenyl)-1H-pyrrole-3-carboxylate

Participants

Reaction Steps

To a cooled (−77° C.) solution of 1M lithium hexamethyldisilazide in THF (102.4 mL, 102.4 mmol) was added 1-[(isocyanomethyl)sulfonyl]-4-methylbenzene (20.0 g, 102.4 mmol) as a solution in THF (100 mL) dropwise (30 min). The solution was allowed to stir for 15 min, and then ethyl (2E)-3-(4-nitrophenyl)acrylate (22.66 g, 102.4 mmol) was added dropwise (1 h) as a solution in THF (250 mL). The reaction was allowed to warm to rt over 17 h and the aqueous saturated sodium bicarbonate solution (200 mL) was added. The product was extracted with ethyl acetate (3×300 mL), and then the combined organic extracts were washed with water (100 mL), dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel chromatography using 0-5% ethylacetate/dichlromethane to afford the desired product (16.65 g, 62%). 1H-NMR (300 MHz, DMSO-d6) δ 11.78 (br s, 1H), 8.15-8.19 (m, 2H), 7.73-7.76 (m, 2H), 7.55-7.79 (m, 1H), 7.19-7.24 (m, 1H), 4.16 (q, J=7.1 Hz, 2H), 1.21 (t, J=7.1 Hz, 3H); HPLC (Method A) 2.90 min; TLC Rf=0.47 (95:5 v/v CH2Cl2-EtOAc).

Provenance & Evidence