N-(tert-Butoxycarbonyl)-4-chloro-L-phenylalanine → (S)-tert-Butyl 4-(4-chlorobenzyl)-1,2,3-oxathiazolidine-3-carboxylate 2,2-dioxide

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Reaction Steps

To a solution of allyl 3-(isoquinolin-6-yl)isoxazol-5-ylcarbamate (0.055 g, 0.19 mmol) in 3 mL of DMF was added cesium carbonate (0.12 g, 0.37 mmol). The mixture was heated to 50° C. (S)-tert-Butyl 4-(4-chlorobenzyl)-1,2,3-oxathiazolidine-3-carboxylate 2,2-dioxide (0.097 g, 0.28 mmol) was added slowly in 0.75 mL of THF. After 30 minutes, the reaction was cooled to room temperature and diluted with 10 mL of EtOAc. 10 mL of 10% HCl was then carefully added. After 30 minutes, the reaction was diluted with 15 mL of 5% aq. NaOH. The biphasic mixture was partitioned and the aqueous portion was extracted twice with 20 mL of EtOAc. The combined organic extracts were washed with twice with 10 mL of water and 15 mL of brine and then dried over MgSO4. Filtration and concentration under reduced pressure, followed by flash chromatography on silica gel (20% to 50% EtOAc/hexanes) afforded the desired adduct (0.095 g, 91% yield) as a yellow solid. (S)-tert-Butyl 4-(4-chlorobenzyl)-1,2,3-oxathiazolidine-3-carboxylate 2,2-dioxide was prepared in a similar manner as that described for (S)-tert-butyl 4-(4-(trifluoromethyl)benzyl)-1,2,3-oxathiazolidine-3-carboxylate-2,2-dioxide in Scheme 1, using (S)-3-(4-chlorophenyl)-2-(tert-butoxycarbonylamino)propanoic acid commercially available from 3B Scientific Corporation Product List (Order Number 3B3-011434) instead of (S)-2-(tert-butoxycarbonylamino)-3-(4-(trifluoromethyl)phenyl)propanoic acid.

Provenance & Evidence