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

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of (R)-tert-butoxycarbonylamino-(4-hydroxy-phenyl)-acetic acid (1.4 g, 5.24 mmol) in dry N,N-dimethylformamide (25 mL) at 0° C. under an atmosphere of dry argon was added sodium hydride (60% suspension in mineral oil) (290 mg, 0.12 mmol) and the mixture stirred at 0° C. for 15 minutes. 2,5-Dichloro-benzenesulfonic acid (R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl ester (2.14 mmol, 6.29 mmol) was added to the reaction mixture to form a yellow solution which was stirred at ambient temperature for 5 minutes before warming to 100° C. for 10 minutes. The reaction mixture which by now contained a heavy precipitate was cooled to ambient temperature, diluted with ethyl acetate, cooled to 0° C. and treated with an equal volume of water. The stirred mixture was acidified to pH≈4 with 1 M aqueous hydrochloric acid. The organic layer was separated and the aqueous layer extracted with ethyl acetate. The combined organic layers were washed with water (three times), dried over sodium sulfate, filtered through a thin pad of silica gel and concentrated in vacuo to give (R)-tert-butoxycarbonylamino-[4-((S)-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-phenyl]-acetic acid as a pale yellow solid foam which was of adequate purity for subsequent use in step 33-G without additional purification (1.96 g, 96%). HR-MS: calcd for C25H26FlN4O5 [M+H+] 609.1005. Found 609.1006.

Provenance & Evidence