Sodium hydride → N-(Trimethylsilyl)methyl benzazepine

Participants

Reaction Conditions

Reaction Steps

60% sodium hydride in mineral oil (39 mg, 0.96 mmol, 1.3 equiv) was added to a stirred solution of benzazepine 25 (180 mg, 0.74 mmol, 1.0 equiv) in tetrahydrofuran (9.3 mL) at 25° C. The resulting brown suspension was stirred at 25° C. for 1 h. (Iodomethyl)trimethylsilane (0.55 mL, 3.7 mmol, 5.0 equiv) was added via syringe at 25° C. The reaction vessel was sealed under argon and heated to 50° C. via oil bath for 30 m. The reaction mixture was cooled to 25° C. and approximately 50% of the solvent volume was removed by sweeping with nitrogen. The crude reaction mixture was loaded directly onto a column and purified by silica gel column chromatography (5% triethylamine in ethyl acetate) to afford 31 (151 mg, 62% yield) as an off-white amorphous solid. Rf=0.41 (5% triethylamine in ethyl acetate); 1H NMR (500 MHz, CDCl3) δ 7.76 (s, 1H, ArH), 6.48 (s, 1H, ArH), 5.89 (s, 2H, OCH2O), 3.56 (m, 2H, CH2), 3.02 (br s, 2H, NCH2Si), 2.91 (m, 2H, CH2), 2.59 (m, 2H, CH2), 2.49 (m, 2H, CH2), 0.13 (s, 9H, Si(CH3)3); 13C NMR (125 MHz, CDCl3) δ 200.86, 169.37, 146.18, 145.19, 132.71, 127.17, 110.46, 109.47, 108.06, 100.92, 57.78, 46.78, 36.22, 33.37, 28.08, −1.26; IR (neat film) 2953 (w, br), 1647 (w), 1556 (s), 1488 (m), 1445 (m), 1353 (w), 1248 (m), 1039 (m), 843 (m) cm−1; HRMS (EI) m/z: Calcd for C18H23NO3Si (MH+) 330.1525, observed 330.1525.

Provenance & Evidence