2-Mercaptoethanol → tert-butyl (3R,5S)-3-(morpholin-4-ylcarbonyl)-5-(propylamino)piperidine-1-carboxylate

HRID 1260113Notes

Reaction equation

HRID 1260113 reaction equation
[N:1]1([C:7]([C@@H:9]2[CH2:14][C@H:13]([N:15](S(C3C=CC=CC=3[N+]([O-])=O)(=O)=O)[CH2:16][CH2:17][CH3:18])[CH2:12][N:11]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:10]2)=[O:8])[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.O.[OH-].[Li+].C(O)CS>CN(C=O)C.C(=O)(O)[O-].[Na+]>[N:1]1([C:7]([C@@H:9]2[CH2:14][C@H:13]([NH:15][CH2:16][CH2:17][CH3:18])[CH2:12][N:11]([C:31]([O:33][C:34]([CH3:35])([CH3:37])[CH3:36])=[O:32])[CH2:10]2)=[O:8])[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1

Participants

6

Reactant 3

HCID 15672-MercaptoethanolHCID 168937Lithium hydroxide, monohydrateHCID 58355213tert-butyl (3R,5S)-3-(morpholin-4-ylcarbonyl)-5-{[(2-nitrophenyl)sulfonyl](propyl)amino}piperidine-1-carboxylate

Product 1

HCID 58355640tert-butyl (3R,5S)-3-(morpholin-4-ylcarbonyl)-5-(propylamino)piperidine-1-carboxylateYield 71.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 516892Sodium BicarbonateSolvent

Procedure

tert-Butyl (3R,5S)-3-(morpholin-4-ylcarbonyl)-5-{[(2-nitrophenyl)sulfonyl](propyl)amino}piperidine-1-carboxylate (4.02 g) and lithium hydroxide monohydrate (1.56 g) were dissolved in DMF (20 ml), thioglycol acid (1.3 ml) was added at room temperature, and the mixture was stirred for 2 days at room temperature. The reaction mixture was diluted with aqueous sodium bicarbonate, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was subjected to basic silica gel column chromatography, and a fraction eluted with ethyl acetate-hexane (1:9-10:0) was concentrated under reduced pressure. The residue was diluted with 10% aqueous citric acid solution, and washed with ethyl acetate. The aqueous layer was neutralized with aqueous sodium bicarbonate and extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure to give the object product (1.89 g).

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe extract was washed with saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. customThe solvent was evaporated under reduced pressure
  5. washa fraction eluted with ethyl acetate-hexane (1:9-10:0)
  6. concentrationwas concentrated under reduced pressure
  7. additionThe residue was diluted with 10% aqueous citric acid solution
  8. washwashed with ethyl acetate
  9. extractionextracted with ethyl acetate
  10. washThe extract was washed with saturated brine
  11. dry with materialdried over anhydrous magnesium sulfate
  12. customThe solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-6fe950ff2fae4373b02e0918c26e531a
Source dataset
uspto-grants-2013_06
Patent number
US08466282B2

Reaction notes

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