Benzyl chloromethyl ether → HCID 67696645, compound

Participants

Reaction Steps

To a stirring solution of 1.0 g (2.18 mmol) of 2-(2,4-Dioxo-5-phenyl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl)-N-isopropyl-N-(4-methoxy-phenyl) acetamide, prepared as in Intermediate 4, in 10 mL of DMF at -5° C. is added 2.40 mL (2.40 mmol, 1.1 equiv) of a 1.0M solution of NaN(TMS)2 in THF. The resulting solution is stirred 5 min, and then 530 μL (3.05 mmol, 1.4 equiv) of chloromethyl benzyl ether (80%, tech.) is added neat. The resulting solution is stirred for 1 h at RT then quenched with 5 mL of H2O. The reaction mixture is poured into 100 mL of EtOAc and extracted with H2O (2×80 mL). The organic layer is separated, dried (MgSO4), and the solvents removed in vacuo. Purification by silica gel flash column chromatography using a gradient elution of hexane/EtOAc 4/1 to hexane/EtOAc 1/2 as eluent afforded 500 mg of the title compound as a white solid, along with 320 mg of recovered starting benzodiazepine: mp. 203°-204° C.; 1H NMR (CDCl3, 400 MHz) δ7.37-7.18 (m, 13H), 7.10 (m, 2H), 6.92 (m, 3H), 4.98 (m, 1H), 4.56 (dd, 2H, J=11.8, 22.7), 4.25 (m, 3H), 4.08 (dd, 1H, J=5.0, 9.8), 3.83 (s, 3H), 3.67 (dd, 1H, J=5.0, 7.5), 1.06 (2×d, 6H, J=6.2); low resolution MS (FAB)m/e 578 (MH+), 443, 413, 277, 223; Anal. (C35H35N3O5) Calcd. C, 72.77; H, 6.11; N, 7.27 Found C, 71.62; H, 6.06; N, 7.10.

Provenance & Evidence