Sodium Iodide → 2-Naphthylmethyl 3-methyl-7-[2-phenyl-2-(4-ethyl-2,3-dioxopiperazine-1-carboxamido)acetamido]ceph-3-em-4-carboxylate

Participants

Reaction Steps

3-Methyl-7-[2-phenyl-2-(4-ethyl-2,3-dioxopiperazine-1-carboxamido)acetamido]ceph-3-em-4-carboxylic acid (4.48 g., 8.7 mmoles) was dissolved in 30 ml. of dimethylformamide. Triethylamine (8.79 mg., 8.7 mmoles) was added and the mixture stirred for 30 minutes. Potassium bicarbonate (1.74 g., 17.4 mmoles) was added and stirring continued for 1 hour. Finally sodium iodide (1.3 g., 8.7 mmoles) and 2-(bromomethyl)naphthalene (2.11 g., 9.6 mmoles) were added (a slight exotherm was noted), and the mixture allowed to stir about 16 hours at room temperature. Since tlc (9:1 acetone:water) monitoring of the reaction mixture over the next 8 hours indicated that reaction had ceased prior to complete conversion to the ester, one-tenth quantities of potassium bicarbonate, sodium iodide and 2-(bromomethyl)naphthalene were added and the reaction allowed to proceed for a further 16 hours. The reaction mixture was diluted with 1:1 ethyl acetate:water, and the organic layer was separated and back-washed several times with water. The organic phase was layered with fresh water, the pH lowered to 2.5, and the organic layer separated, washed with several portions of water, washed with brine, dried over anhydrous magnesium sulfate, filtered and evaporated in vacuo to yield 2-naphthylmethyl 3-methyl-7-[2-phenyl-2-(4-ethyl-2,3-dioxopiperazine-1-carboxamido)acetamido]ceph-3-em-4-carboxylate [4.8 g., 84%; Rf 0.39 (ethyl acetate)].

Provenance & Evidence