Dicyclohexylcarbodiimide → 9-(1,3-benzodioxol-5-yl)-8-(benzyloxymethyl)-N-(3-benzyloxypropyl)benzo[g][1,3]benzodioxole-7-carboxamide

Participants

Reaction Steps

A 60% sodium hydride dispersion in mineral oil (4 g, 0.1 mol) in a small portion at room temperature was added to a stirred solution of 3-amino-1-propanol (7.51 g, 0.1 mol) in THF (150 mL). The mixture was stirred for 30 min under nitrogen, and benzyl bromide (11.9 mL, 0.1 mol) was added. The mixture was stirred for 10 h at room temperature, and concentrated in vacuo. The residue was partitioned between 1 N aqueous HCl solution and CH2Cl2. The aqueous layer was adjusted to pH 10 with 10% aqueous NaOH solution, and extracted with CH2Cl2 (3×100 mL). The extract was dried over MgSO4 and concentrated in vacuo. The residue was purified by silica gel column chromatography using CH2Cl2/MeOH (3:1 to 2:1, v/v) to give 3-(benzyloxy)propylamine (1.37 g, 8.3%) as a yellow oil. 1,3-Dicyclohexylcarbodiimide (14.4 mg, 0.07 mmol) in CH2Cl2 (2 mL) at 0° C. was added dropwise to a mixture of 5 (32 mg, 0.07 mmol) and 3-(benzyloxy)propylamine (11.6 mg, 0.07 mmol), and 1-hydroxybenzotriazole hydrate (9.5 mg, 0.07 mmol) in CH2Cl2 (5 mL). The reaction mixture was stirred for 18 h at room temperature and concentrated in vacuo. The residue was purified by silica gel column chromatography using CH2Cl2/MeOH (30:1, v/v) to afford 8 (36 mg, 85%) as a pale yellow liquid. 1H NMR (CDCl3) δ 8.05 (s, 1H, H4), 7.44 (d, 1H, H5, J=8.7 Hz), 7.19-7.28 (m, 11H, H6+2×OCH2Ph), 6.78-6.82 (m, 3H, H2′+H5′+H6′), 6.06 (AB, 2H, 3′,4′-OCH2O—, Δδ=6.9 Hz, J=1.5 Hz), 5.84 (AB, 2H, 7,8-OCH2O—, Δδ=4.2 Hz, J=1.5 Hz), 4.45 (s, 4H, 2×OCH2Pb), 4.38 (s, 2H, 2-CH2OBn), 3.55 (m, 4H, 3-CONHCH2CH2CH2OBn), 1.87 (quintet, 2H, 3-CONHCH2CH2CH2OBn. J=6.3 Hz); MS (FAB, positive) m/z 604 [M+H]+.

Provenance & Evidence