Hydrochloric Acid → Ethyl trans-4-hydroxy-L-prolinate hydrochloride

Participants

Reaction Steps

Trans-4-hydroxy-L-proline was treated with EtOH and HCl gas, and the mixture was evaporated to give trans-4-hydroxy-L-proline ethyl ester hydrochloride. This product was treated with TsCl in pyridine to give, after aqueous workup, N-(toluene-4-sulfonyl)-trans-4-(TsO)-L-proline ethyl ester. This product was treated with NaN3 in DMF and H2O to give, after aqueous workup and flash chromatography, N-(toluene-4-sulfonyl)-cis-4-azido-L-proline ethyl ester. This product was treated with NaOH in CH3OH and H2O to give, after acidification, extraction, drying with MgSO4, filtration and evaporation, N-(toluene-4-sulfonyl)-cis-4-azido-L-proline. This product was treated with 10% Pd on C in THF, AcOH and H2O, and the mixture was shaken under 50 psi H2. The mixture was filtered through Celite and evaporated to give N-(toluene-4-sulfonyl)-cis-4-anino-L-proline. This product was treated with Boc2O and Et3N in t-BuOH and H2O to give, after evaporation, acidification, extraction, drying with MgSO4, filtration, and evaporation, N-(toluene-4-sulfonyl)-cis-4-(t-butoxycarbonylamino)-L-proline. This product was treated with HCl.Phe-O-t-Bu, BOP, and NMM in DMF to give, after aqueous workup and flash chromatography, N-(toluene-4-sulfonyl)-cis-4-(t-butoxycarbonylamino)-Pro-Phe-O-t-Bu. This product was treated with TFA to give after evaporation the trifluoroacetate salt of the title compound as a clear oil.

Provenance & Evidence