p-Toluenesulfonic acid monohydrate → 1-N-[3-(thiazol-4-yl)-L-alanyl]-(2R)-2-methylpyrrolidine di-p-toluenesulfonate

HRID 655983Notes

Reaction equation

HRID 655983 reaction equation
C(OC([NH:8][C@H:9]([C:16]([N:18]1[CH2:22][CH2:21][CH2:20][C@H:19]1[CH3:23])=[O:17])[CH2:10][C:11]1[N:12]=[CH:13][S:14][CH:15]=1)=O)(C)(C)C.O.[C:25]1([CH3:35])[CH:30]=[CH:29][C:28]([S:31]([OH:34])(=[O:33])=[O:32])=[CH:27][CH:26]=1.C(OCC)(=O)C.Cl>C(OCC)(=O)C>[C:25]1([CH3:35])[CH:26]=[CH:27][C:28]([S:31]([OH:34])(=[O:32])=[O:33])=[CH:29][CH:30]=1.[C:25]1([CH3:35])[CH:26]=[CH:27][C:28]([S:31]([OH:34])(=[O:32])=[O:33])=[CH:29][CH:30]=1.[S:14]1[CH:15]=[C:11]([CH2:10][C@@H:9]([C:16]([N:18]2[CH2:22][CH2:21][CH2:20][C@H:19]2[CH3:23])=[O:17])[NH2:8])[N:12]=[CH:13]1

Participants

5

Reactant 3

HCID 521998p-Toluenesulfonic acid monohydrateHCID 21866389Hydrogen chloride-ethyl acetateHCID 866181281-N-[N-(tert-butoxycarbonyl)-3-(thiazol-4-yl)-L-alanyl]-(2R)-2-methylpyrrohdine

Product 1

HCID 867614501-N-[3-(thiazol-4-yl)-L-alanyl]-(2R)-2-methylpyrrolidine di-p-toluenesulfonateYield 62%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

Compound (3) (33.77 g, 99.48 mmol) and p-toluenesulfonic acid hydrate (37.85 g, 199 mmol) were dissolved in ethyl acetate (101 ml) and the solution was cooled with ice. To the mixture, 4 mol/L solution of hydrogen chloride-ethyl acetate (125 ml) was added, and the mixture was stirred for 2 hours 45 minutes. After the mixture was concentrated under reduced pressure, methanol was added to the residue. The mixture was concentrated. Methanol-toluene (1:1) was added to the residue and concentrated under reduced pressure to give crystalline residue. The residue was washed with acetone and filtered to give compound (4) as crystals (36 g, 62%). After the mother liquor was concentrated under reduced pressure, methanol and toluene were added to the residue and concentrated. Obtained crystalline residue was washed with acetone to give compound (4) (10.67 g, 18.4%).

Workup

  1. temperaturethe solution was cooled with ice
  2. concentrationAfter the mixture was concentrated under reduced pressure, methanol
  3. additionwas added to the residue
  4. concentrationThe mixture was concentrated
  5. additionMethanol-toluene (1:1) was added to the residue
  6. concentrationconcentrated under reduced pressure
  7. customto give crystalline residue
  8. washThe residue was washed with acetone
  9. filtrationfiltered

Sources & evidence

ORD record
ord-ed58bd3268c749c7bafaa9b28170e7dd
Source dataset
uspto-grants-2011_12
Patent number
US08071633B2

Reaction notes

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