Tetrahydrofuran → cyclopropyl[4-(2-{2-[(2R)-2-methyl-1-pyrrolidinyl]ethyl}-1-benzofuran-5-yl)phenyl]methanone

Participants

Reaction Conditions

Reaction Steps

The product from Example 1D (330 mg, 1.0 mmol) was dissolved into tetrahydrofuran (1 mL), treated with ˜0.7 M cyclopropylmagnesium bromide in tetrahydrofuran (2 mL, ˜1.4 mmol) and copper(I) iodide (a few milligrams), and heated at 45° C. for one day and at 60° C. for two days. The reaction was brought to room temperature, quenched with 0.4 M aqueous hydrochloric acid (5 mL), and extracted with EtOAc. The organic phase was washed consecutively with 0.5 M aqueous dipotassium hydrogen phosphate and brine, dried (Na2SO4), concentrated, and purified by HPLC [Waters Nova-Pak HR C18 column (40 mm×100 mm, 6 μm particle size) using a gradient of 10% to 100% MeCN/0.1% aqueous TFA over 12 min (15 min run time) at a flow rate of 70 mL/min.] to provide the title compound as a powder (44% yield). MS (ESI APCI) m/z 374 (M+H)+; 1HNMR (300 MHz, CD3OD) δ 1.06-1.21 (m, 7H), 1.38-1.53 (m, 1H), 1.73-1.86 (m, 2H), 1.94-2.08 (m, 1H), 2.23-2.34 (m, 1H), 2.40-2.59 (m, 2H), 2.83-3.15 (m, 3H), 3.19-3.34 (m, 2H), 6.62 (s, 1H), 7.51 (d, 1H), 7.56 (dd, 1H), 7.76-7.85 (m, 3H), 8.12 (d, 2H).

Provenance & Evidence