Ammonium Hydroxide → N-Acetylcysteine amide

HRID 1048867Notes

Reaction equation

HRID 1048867 reaction equation
[C:1]([NH:4][C@@H:5]([CH2:10][SH:11])[C:6](OC)=[O:7])(=[O:3])[CH3:2].[OH-].[NH4+:13]>C1(C)C=CC=CC=1.ClCCl.CO>[C:1]([NH:4][C@@H:5]([CH2:10][SH:11])[C:6]([NH2:13])=[O:7])(=[O:3])[CH3:2]

Participants

5

Reactant 2

HCID 14923Ammonium HydroxideHCID 6542158L-Cysteine, N-acetyl-, methyl ester

Product 1

HCID 10176265N-Acetylcysteine amideYield 52%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 21226129Dichloromethane methanolSolvent

Procedure

45a (53.4 g, 0.30 mol) was diluted with 250 mL of toluene and 200 mL of ammonium hydroxide. The mixture was stirred at room temperature overnight then concentrated. The resulting residue was suspended in 250 mL of acetonitrile/H2O (9.3:1) and stirred at room temperature until the insoluble material formed a viscous paste. The solvent was decanted then concentrated to give a viscous liquid. The crude product was taken up in dichloromethane/methanol (8.5:1) and passed through a silica gel column eluting with dichloromethane/methanol (8.5:1). Fractions containing the least polar UV-active component were combined and concentrated to give 25 g (52%) of (R)-2-acetamido-3-mercaptopropanamide as white solid. 1HNMR (DMSO-d6) δ 8.0 (d, 1H), 7.41 (s, 1H), 7.13 (s, 1H), 4.33 (m, 1H), 2.76 (m, 1H), 2.65 (m, 1H), 2.22 (m, 1H), 1.88 (s, 3H).

Workup

  1. concentrationthen concentrated
  2. stirringstirred at room temperature until the insoluble material
  3. customformed a viscous paste
  4. customThe solvent was decanted
  5. concentrationthen concentrated
  6. customto give a viscous liquid
  7. washeluting with dichloromethane/methanol (8.5:1)
  8. additionFractions containing the least polar UV-active component
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-4687967ac9794296a71bf7e1be0e6568
Source dataset
uspto-grants-2016_07
Patent number
US09382211B2

Reaction notes

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