Hydrochloric Acid → (R)-tert-Butoxycarbonylamino-[4-((S)-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-phenyl]-acetic acid

Participants

Reaction Conditions

Reaction Steps

(R)-tert-Butoxycarbonylamino-(4-hydroxy-phenyl)-acetic acid (200 mg, 0.75 mmol) was dissolved in anhydrous N,N-dimethylformamide (4 mL) followed by the addition of sodium hydride (60% dispersion in mineral oil) (63 mg, 1.57 mmol) at room temperature. The reaction was stirred for 30 minutes followed by the dropwise addition of methanesulfonic acid (R)-2,2-dimethyl-[1,3]dioxolan4-ylmethyl ester (189 mg, 0.90 mmol) dissolved in N,N-dimethylformamide (2 mL) at room temperature. The mixture was heated to 100° C. overnight. The reaction was cooled to room temperature, acidified to pH=4 with 0.2 M aqueous hydrochloric acid, poured into ethyl acetate and diluted with water. The organic layer was washed with brine and dried over sodium sulfate. Removal of solvents gave (R)-tert-butoxycarbonylamino-[4-((S)-2,2-dimethyl-[1,3]dioxolan4-ylmethoxy)-phenyl]-acetic acid as a foam (280 mg, 98%).

Provenance & Evidence