Dimethylformamide → (R)-tert-butoxycarbonyl amino-(4-dimethylcarbamoyl methoxy-phenyl)-acetic acid

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Reaction Steps

Prepared by the same method as described in example 1, step 1-G for the preparation of (R)-tert-butoxycarbonylamino-[4-(2-tert-butoxy-ethoxy)-phenyl]-acetic acid except that 2-chloro-N,N-dimethyl-acetamide was used in place of 2-(2-iodo-ethoxy)-2-methyl-propane and the preparation performed as follows: Sodium hydride (0.88 g, 22 mmol, 60% in mineral oil) was added portionwise to a stirred and cooled (ice bath) solution of (S)-tert-butoxycarbonylamino-(4-hydroxy-phenyl)-acetic acid (2.67 g, 10 mmol) in N,N-dimethylformamide (50 mL). 2-Chloro-N,N-dimethyl-acetamide (1.22 g, 10 mmol) was added and the mixture was stirred for three days. The mixture was diluted with water and extracted with ether. The aqueous layer was acidified to pH=2 and extracted with ethyl acetate. The combined organic extracts were washed with water, brine, dried over sodium sulfate, filtered and following evaporation of the solvents (S)-tert-butoxycarbonylamino-(4-dimethylcarbamoylmethoxy-phenyl)-acetic acid was obtained as a white solid (2.68 g, 76%). HR-MS: calcd for C31H29BrClN5O4 [M+H+] 650.1164. Found 650.1166.

Provenance & Evidence