Sodium Carbonate → (2S)-1-(4-methylbenzenesulfonyl)pyrrolidine-2-carboxylic acid

HRID 890577

Reaction equation

HRID 890577 reaction equation
Cl.C[O:3][C:4](=[O:10])[C@@H:5]1[CH2:9][CH2:8][CH2:7][NH:6]1.Cl[S:12]([C:15]1[CH:23]=[CH:22][C:18]([C:19](O)=O)=[CH:17][CH:16]=1)(=[O:14])=[O:13].C(=O)([O-])[O-].[Na+].[Na+].FC(F)(F)C(OC1C(F)=C(F)C(F)=C(F)C=1F)=O>O.CN(C)C=O.ClCCl.C(N(CC)CC)C.N1C=CC=CC=1>[S:12]([N:6]1[CH2:7][CH2:8][CH2:9][C@H:5]1[C:4]([OH:3])=[O:10])([C:15]1[CH:23]=[CH:22][C:18]([CH3:19])=[CH:17][CH:16]=1)(=[O:14])=[O:13]

Participants

10

Reactant 4

HCID 10340Sodium CarbonateHCID 823854-(Chlorosulfonyl)benzoic acidHCID 2733200methyl L-prolinate hydrochlorideHCID 4327891Pentafluorophenyl Trifluoroacetate

Product 1

HCID 691957(2S)-1-(4-methylbenzenesulfonyl)pyrrolidine-2-carboxylic acid

Reagents, catalysts & solvents 5

HCID 962WaterSolventHCID 1049PyridineSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Procedure

N-tosyl-proline derivatives were synthesized as follows. Proline methyl ester hydrochloride was reacted with 4-(chlorosulfonyl)benzoic acid and sodium carbonate in water. The product was converted to the pentafluorophenyl ester by reacting it with pentafluorophenyl trifluoroacetate and pyridine in N,N-dimethylformamide, and purified via flash chromatography. This activated ester was then reacted with the methyl-ester of glutamate (or any of the other amino acids tested) in the presence of triethylamine and dichloromethane, the product purified by flash chromatography, and the methyl esters hydrolyzed with lithium hydroxide in water. The final products were purified via reverse-phase HPLC and lyophilized.

Workup

  1. custompurified via flash chromatography
  2. customThis activated ester was then reacted with the methyl-ester of glutamate (or any of the other amino acids
  3. customthe product purified by flash chromatography
  4. customThe final products were purified via reverse-phase HPLC

Sources & evidence

ORD record
ord-9f53c9452f294edf8695ae1906d4800c
Source dataset
uspto-grants-2006_02
Patent number
US06998233B2

Linked notes

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