Ethyl bromoacetate → [2-(3-Ethoxy-phenoxymethyl)-3-isobutyl-3H-benzimidazol-5-yloxy]-acetic acid ethyl ester

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Reaction Steps

A 100 mL flask fitted with a stir-bar and septum with an Ar inlet was charged with benzimidazole 66b (3.00 g, 8.81 mmol) and DMF (35 mL). To the resultant solution was added K2CO3 (1.83 g, 13.2 mmol) followed by ethyl bromoacetate (1.62 g, 1.07 mL, 9.69 mmol). The mixture was stirred at rt overnight. The solids were then filtered off and rinsed with EtOAc (2×50 mL). The filtrate was washed with saturated NH4Cl (2×75 mL), H2O (2×75 mL), and brine (75 mL) and filtered through phase separation paper. The organic phase was filtered through a plug of silica gel, rinsed with EtOAc (3×100 mL), and concentrated in vacuo to 4.0 g of a brown oil. 1 g of the crude oil was chromatographed on a Biotage MPLC 25+M silica gel column with the product eluting with 30-36% EtOAc in hexanes. The product fractions were concentrated to give 975 mg of Compound #13 as a yellow oil (100%). 1H NMR (300 MHz, CDCl3): δ 7.69 (d, 1H), 7.20 (t, 1H), 6.93 (dd, 1H), 6.88 (d, 1H), 6.67 (dd, 1H), 6.63 (t, 1H), 6.54 (dd, 1H), 5.32 (s, 2H), 4.70 (s, 2H), 4.29 (qt, 2H), 4.05 (qt, 2H), 4.04 (d, 2H), 2.34 (nonet, 1H), 1.41 (t, 3H), 1.32 (t, 3H), 0.97 (d, 6H) ppm. HPLC analysis (0:10:90 H2O:A1:MeOH) showed a purity of 99% with a retention time of 3.9 min.

Provenance & Evidence