Benzyl Alcohol → HCID 10621119, compound

Participants

Reaction Steps

A solution of the above malonate (3.44 g, 11.6 mmol), SOCl2 (1.0 mL, 13.9 mmol) and DMF (4 drops) in 1,2-dichloroethane (60 mL) was stirred under reflux for 1 h, cooled and evaporated. The residue was dissolved in Me2CO (30 mL) and added dropwise over 10 min to a vigorously stirred solution of sodium azide (2.26 g, 35 mmol) in water (30 mL) and M acetone (100 mL) at 0° C. After a further 30 min at 0° C., EtOAc (100 mL) was added, most of the Me2CO was evaporated, and the EtOAc layer was washed with water, dried (Na2SO4), and evaporated. The residue was dissolved in dry toluene (35 mL) and stirred at reflux for 40 min. Benzyl alcohol (2.2 mL, 21 mmol) was added to the cooled solution and the mixture stirred at 20° C. for 2 h [until a sample spotted on a tlc plate no longer showed the formation of yellow dimethyl (4-amino-2-nitrophenyl)malonate]. The mixture was then evaporated and the residue was distilled in a Kugelrohr (1 mm Hg, 90° C.) to remove excess benzyl alcohol. Flash chromatography on silca gel, eluting with petroleum ether/EtOAc (3:1) gave dimethyl [4-(benzyloxycarbonyl)amino-2-nitrophenyl]malonate as a yellow oil (3.77 g, 81%). 1H NMR (CDCl3) 8.16 (d, J=2.3 Hz, 1 H, H-3), 7.59 (dd, J=8.5, 2.3 Hz, 1 H, H-5), 7.42-7.33 (m, 6 H, H-6 and Ph), 7.11 (s, 1 H, NH), 5.25 (s, 1 H, ArCH), 5.22 (s, 2 H, OCH2Ph), 3.78 (s, 6 H, CO2Me); 13C NMR (CDCl3) d 167.9, (CO2Me), 152.8 (NCO2), 149.0, 139.1, 135.4, 131.9, 128.7, 128.6, 128.4, 122.7, 121.9, 114.6 (aromatic C), 67.6 (OCH2Ph), 53.5 (ArCH), 53.2 (OMe); MS (DEI) m/z 402 (2%, M+), 91 (100%, (C7H7); HRMS calcd. for C19H18N2O8 402.10631, found 402.10594.

Provenance & Evidence