Hydrochloric Acid → HCID 21100012, compound

Participants

Reaction Steps

To an ice-cold solution of 4-aminophenylacetic acid (500 mg, 3.307 mmol) in 1:1 dioxane-water (10 mL) was added a solution of 2 N NaOH (˜2.2 equivalent, pH 9-10). This mixture was treated with benzylchloroformate (0.5 mL, 3.681 mmol) and the solution was allowed to stir in an ice-bath for 2 h. The reaction mixture was acidified with an aqueous solution of 1 N HCl (pH ˜4), extracted with ethyl acetate, dried (Na2SO4), and concentrated in vacuo to give a solid as crude product. Purification of the solid (SiO2, 10:1 CHCl3/MeOH) gave N-Cbz protected phenylacetic acid (856 mg, 91%) as a pure white solid. To make the succinimide active ester, a mixture of N-Cbz protected acid (120 mg, 0.421 mmol), N-hydroxysuccinimide (53 mg 97%, 0.445 mmol), and dicyclohexylcarbodiimide (88 mg, 0.421 mmol) in dry THF (4 mL) was stirred at room temperature under an atmosphere of argon for 2 h. This solution was directly used for preparation of compound 35.

Provenance & Evidence