N-[2-(Isobutylamino)-4-(3-methylbutoxy)phenyl]-2-(3-methoxyphenoxy)acetamide → 1-Isobutyl-2-(3-methoxy-phenoxymethyl)-6-(3-methyl-butoxy)-1H-benzimidazole

Participants

Reaction Steps

A 250 mL flask fitted with a stir-bar, condenser, and an Ar inlet was charged with amine 50b (10.7 g, 25.8 mmol) and AcOH (110 mL). The resultant solution was heated in a 100° C. bath for 3 hr. The mixture was cooled and concentrated in vacuo to an orange solid. The solid was partitioned with EtOAc (150 mL) and saturated NaHCO3 (100 mL). The organic phase was then washed with brine (100 mL), filtered through phase separation paper, and concentrated in vacuo to 10.6 g of a red oil. The oil was chromatographed on silica gel eluting the product with 10-15% EtOAc in hexanes. The product fractions were concentrated in vacuo to give 8.9 g of Compound #2 as an orange oil, which slowly crystallized (87%). 1H NMR (300 MHz, CDCl3): δ 7.66 (d, 1H), 7.22 (t, 1H), 7.27 (t, 1H), 6.93 (dd, 1H), 6.82 (d, 1H), 6.69 (dd, 1H), 6.63 (t, 1H), 6.57 (dd, 1H), 5.32 (s, 2H), 4.06 (t, 2H), 4.04 (d, 2H), 3.81 (s, 3H), 2.36 (nonet, 1H), 1.90 (nonet, 1H), 1.74 (qt, 2H), 1.00 (d, 6H), 0.97 (d, 6H) ppm. HPLC analysis (0:10:90 H2O:A1:MeOH) showed a purity of 98% with a retention time of 5.8 min.

Provenance & Evidence