Methanesulfonyl chloride → HCID 86593806, compound

HRID 1157353Notes

Reaction equation

HRID 1157353 reaction equation
[CH3:1][S:2](Cl)(=[O:4])=[O:3].[C:6]([O:10][C:11]([N:13]1[CH2:21][C@H:19]([OH:20])[CH2:18][C@H:14]1[C:15]([OH:17])=[O:16])=[O:12])([CH3:9])([CH3:8])[CH3:7]>C(Cl)Cl>[S:2]([O:16][C:15](=[O:17])[C@@H:14]1[CH2:18][C@@H:19]([OH:20])[CH2:21][N:13]1[C:11]([O:10][C:6]([CH3:9])([CH3:7])[CH3:8])=[O:12])([CH3:1])(=[O:4])=[O:3]

Participants

4

Reactant 2

HCID 31297Methanesulfonyl chlorideHCID 88804(2S,4R)-4-hydroxy-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acid

Product 1

HCID 86593806HCID 86593806, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Methanesulfonyl chloride (2 eq) was slowly added at 0° C. to a DCM solution of N-(tert-butoxycarbonyl)-hydroxyproline N,O-dimethylhydroxamide and TEA (2 eq). The reaction mixture was stirred for an additional 10 minutes and allowed to aftain room temperature with continued stirring for an additional 45 minutes. The solvent was then evaporated and residue taken in water. It was extracted with ethyl acetate (twice) and the combined organic layer was washed with brine and dried over sodium sulfate. The solvent was evaporated and residue dried under vacuum to give O-mesyl N-(tert-butoxycarbonyl)-hydroxyproline N,O-dimethylhydroxamide. The yield from this reaction approached 100%. To a suspension of sodium hydride (2 eq) in DMF was added an aromatic alcohol (2 eq) taken in DMF under vigorous stirring. After completion of the hydrogen release, the solution was added to the DMF solution of O-mesyl N-(tert-butoxycarbonyl)-hydroxyproline N,O-dimethylhydroxamide and stirred for 16 hours. The reaction temperature then was raised to 90° C. with continued stirring for 24-48 hours. After cooling, the reaction mixture was poured into water and extracted twice with ethyl acetate. The combined organic layer was washed with water (twice), brine (once), and dried over sodium sulfate. The solvent was evaporated and product purified as described in Example 7, Method A.

Workup

  1. customto aftain room temperature
  2. stirringwith continued stirring for an additional 45 minutes
  3. customThe solvent was then evaporated
  4. extractionIt was extracted with ethyl acetate (twice) and the combined organic layer
  5. washwas washed with brine
  6. dry with materialdried over sodium sulfate
  7. customThe solvent was evaporated
  8. customresidue dried under vacuum

Sources & evidence

ORD record
ord-ea3f9c71c0cb470f8c54100e90567a81
Source dataset
uspto-grants-2010_10
Patent number
US07807678B2

Reaction notes

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