Hydrochloric Acid → Ethyl trans-4-hydroxy-L-prolinate hydrochloride
Reaction equation
[OH:1][C@H:2]1[CH2:6][NH:5][C@H:4]([C:7]([OH:9])=[O:8])[CH2:3]1.[ClH:10].[CH3:11][CH2:12]O>>[ClH:10].[CH2:11]([O:8][C:7](=[O:9])[C@@H:4]1[CH2:3][C@@H:2]([OH:1])[CH2:6][NH:5]1)[CH3:12]Participants
Procedure
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.
Workup
- customthe mixture was evaporated
Sources & evidence
- ORD record
- ord-b896703341214070b5926c88575aacfe
- Source dataset
- uspto-grants-2002_03
- Patent number
- US06362341B1
Reaction notes
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