4-Chloro-o-anisic acid → (2-(4-Chloro-2-methoxybenzoyl)-1'H-1,3'-bipyrrol-2'-yl)(2-methoxyphenyl)methanone

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Reaction Steps

Into a solution of 4-chloro-2-methoxybenzoic acid (125 mg, 0.67 mmol, 1.2 eq.) in benzene (1.5 mL), SOCl2 (1.5 mL) was added at room temperature and the resulting solution was refluxed for 2 h. The reaction mixture was concentrated under vacuum to generate 4-chloro-2-methoxybenzoyl chloride which was used directly in the next step without purification. A solution of 4-chloro-2-methoxybenzoyl chloride in DCM (2 mL) was added to a slurry of AlCl3 (96 mg, 1.3 eq.) in DCM (2.5 mL) at 0° C. and then a solution of (e) (150 mg, 0.56 mmol, 1.0 equiv) in DCM (1.5 mL) was added dropwise. The resulting solution was allowed to warm to room temperature and stirred overnight. A saturated solution of NaHCO3 (10 mL) and DCM (10 mL) was then added and the resulting mixture was stirred for 1 h, and then filtered though Celite®. The mixture was extracted with DCM (2×10 mL), the organic layer was dried over anhydrous Na2SO4, and purified by flash column chromatography (hexanes:EtOAc) to afford 172 mg of (h) as a white solid, 70% yield. 1H NMR (400 MHz, CDCl3) δ 9.83 (s, 1H), 7.22-7.14 (m, 2H), 7.12 (d, J=7.8 Hz, 1H), 7.04 (t, J=3.0 Hz, 1H), 6.95-6.88 (m, 2H), 6.73-6.63 (m, 3H), 6.31 (dd, J=4.0, 1.7 Hz, 1H), 6.27 (t, J=2.8 Hz, 1H), 5.83 (dd, J=4.0, 2.6 Hz, 1H), 3.77 (s, 3H), 3.69 (s, 3H).

Provenance & Evidence