Sodium bis(trimethylsilyl)amide → HCID 69223435, compound

Participants

Reaction Steps

A solution of 2-(2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-1H-1,5-diazepin-1-yl)-N-isopropyl-N-(4-methoxyphenyl)acetamide (12p, 1.500 g) in anhydrous DMF (15 mL) under argon was cooled to 0-5° C. Sodium bis(trimethylsilyl)amide (0.6 M in toluene, 7.68 mL) was added via syringe followed 5 minutes later by chloromethyl 2-(trimethylsilyloxy)-1-ethyl ether (0.815 mL). After approximately 10 min., the reaction was quenched with glacial acetic acid and evaporated in vacuo. The residue was partitioned between ethyl acetate and water. The layers were separated and the aqueous layer was back-extracted twice with ethyl acetate. The combined organic layers were dried over anhydrous MgSO4, filtered and evaporated in vacuo. The crude product was purified on flash grade silica gel eluting with 2:5 ethyl acetate/hexane. Fractions containing the product were combined, evaporated in vacuo and dried under high vacuum to provide 2-[2,4-dioxo-5-phenyl-3-[2-(trimethylsilyloxy)-1-ethoxymethylene]-2,3,4,5-tetrahydro-1H-1,5-diazepin-1-yl]-N-isopropyl-N-(4-methoxyphenyl)acetamide(12q, 1.236 g) as a foam. 1H NMR (400 MHz, CDCl3) 0.00 (s, 9H), 0.95 (m, 2H), 1.04 (d, J=6 Hz, 3H), 1.06 (d, J=6 Hz, 3H), 3.62 (m, 3H), 3.83 (s, 3H), 3.91 (d, J=2 Hz, 2H), 4.02 (dd, J=5,10Hz, 1H), 4.15 (dd, J=8,10Hz, 1H), 4.95 (m, 1H), 5.93 (d, J=6 Hz, 1H), 5.99 (d, J=6 Hz, 1H), 6.94 (m, 2H), 7.11 (m, 2H), 7.33 (m, 5H).

Provenance & Evidence