4-Toluenesulfonyl chloride → HCID 53913276, compound

HRID 1356865Notes

Reaction equation

HRID 1356865 reaction equation
S(Cl)(C1C=CC(C)=CC=1)(=O)=O.[N-]=[N+]=[N-].[Na+].C([O:18][C:19](=[O:38])[C@@H:20]1[CH2:24][C@H:23]([N:25]=[N+]=[N-])[CH2:22][N:21]1[S:28]([C:31]1[CH:36]=[CH:35][C:34]([CH3:37])=[CH:33][CH:32]=1)(=[O:30])=[O:29])C.[OH-].[Na+]>N1C=CC=CC=1.CN(C=O)C.O.CO>[C:34]1([CH3:37])[CH:33]=[CH:32][C:31]([S:28]([N:21]2[CH2:22][C@@H:23]([NH2:25])[CH2:24][C@H:20]2[C:19]([OH:38])=[O:18])(=[O:30])=[O:29])=[CH:36][CH:35]=1

Participants

9

Reactant 4

HCID 73974-Toluenesulfonyl chlorideHCID 14798Sodium HydroxideHCID 33557Sodium AzideHCID 18714243HCID 18714243, compound

Product 1

HCID 53913276HCID 53913276, compound

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolvent2×HCID 1049PyridineSolventHCID 6228DimethylformamideSolvent

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-amino-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, arid 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

  1. customto give
  2. customto give
  3. customto give
  4. extractionafter acidification, extraction
  5. dry with materialdrying with MgSO4, filtration and evaporation, N-(toluene-4-sulfonyl)-cis-4-azido-L-proline
  6. additionThis product was treated with 10% Pd on C in THF
  7. filtrationThe mixture was filtered through Celite
  8. customevaporated

Sources & evidence

ORD record
ord-97914270d8b946c09c43d41405900ac3
Source dataset
uspto-grants-2003_07
Patent number
US06586602B2

Reaction notes

Loading…