1,3-Diethyl 2-oxopropanedioate → 1-Ethyl-5-trifluoromethanesulfonyl-1H-benzoimidazole-2-carboxylic acid

Participants

Reaction Conditions

Reaction Steps

N1-Ethyl-4-trifluoromethanesulfonyl-benzene-1,2-diamine (134 mg, 0.50 mmol) and 2-oxo-malonic acid diethyl ester (91 μL, 1.2 equiv) were dissolved in 0.7 mL dry pentanol and heated to reflux for 24 h. The reaction mixture was then evaporated by blowing with a stream of nitrogen while heating, the oil was then placed under full vacuum for at least 20 h whereupon a low melting solid began to form. 1-Ethyl-5-trifluoromethanesulfonyl-1H-benzoimidazole-2-carboxylic acid pentyl ester 1HNMR (400 MHz, d6-DMSO) δ 8.52 (d, J=2.0 Hz, 1H), 8.30 (dd, J=9.2, 2.0 Hz, 1H), 8.07 (d, J=9.2 Hz, 1H), 4.37 (t, J=6.6 H 4.31 (q, J=7.2 Hz, 2H), 1.71 (m, 2H), 1.37 (m, 4H), 1.27 (t, J=7.4 Hz, 3H), 0.89 (T, J=7.0 Hz, 3H); LCMS-APCI m/z 393 [M+1]+. This pentyl ester was used directly (85 mg, 0.217 mmol) and dissolved in warm ethanol (3 mL) with the addition of 1 M sodium hydroxide (1 mL). The reaction mixture was warmed to 40° C. and stirred for 2 h. The reaction mixture was then partially evaporated by blowing with a stream of nitrogen and transferred to a vial containing chloroform and water. The two phases were shaken together, the organic phase was removed, and the process repeated once with additional chloroform. To the aqueous phase was added ethyl acetate, the mixture was acidified with 3 M aqueous hydrochloric acid to pH 2.5, and the organic phase was separated, washed with saturated brine, dried (Na2SO4) and evaporated to yield the acid 42: 1HNMR (400 MHz, d6-DMSO) 8 14.3 (br s, 1H), 8.51 (d, J=2.35 Hz, 1H), 8.30 (dd, J=9.06, 2.28 Hz, 1H), 8.07 (d, J=9.09 Hz, 1H), 4.31 (q, J=7.14 Hz, 2H), 1.28 (t, J=7.10 Hz, 3H); LCMS-APCI m/z [M−1]− 321.

Provenance & Evidence