4-Methylmorpholine → (2R)-2-(tert-Butoxycarbonylamino)-3-(4-methylbenzylthio)propionic acid methylamide

HRID 1003650Notes

Reaction equation

HRID 1003650 reaction equation
[CH3:1][N:2]1CCOCC1.ClC(OCC(C)C)=O.[C:16]([O:20][C:21]([NH:23][C@@H:24]([CH2:28][S:29][CH2:30][C:31]1[CH:36]=[CH:35][C:34]([CH3:37])=[CH:33][CH:32]=1)[C:25](O)=[O:26])=[O:22])([CH3:19])([CH3:18])[CH3:17].C(=O)([O-])O.[Na+]>O1CCCC1>[CH3:1][NH:2][C:25](=[O:26])[C@@H:24]([NH:23][C:21]([O:20][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:22])[CH2:28][S:29][CH2:30][C:31]1[CH:36]=[CH:35][C:34]([CH3:37])=[CH:33][CH:32]=1

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 516892Sodium BicarbonateHCID 7010551N-alpha-t-Butyloxycarbonyl-S-(4-methyl-benzyl)-L-cysteine

Product 1

HCID 15453678(2R)-2-(tert-Butoxycarbonylamino)-3-(4-methylbenzylthio)propionic acid methylamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of N-methylmorpholine (0.217 ml) and isobutyl chloroformate (0.256 ml) in tetrahydrofuran (5 ml) is added to a solution of (2R)-2-(tert-butoxycarbonylamino)-3-(4-methylbenzylthio)propionic acid (reference compound No. 3-1, 700 mg) in tetrahydrofuran (15 ml) under a nitrogen atmosphere and freezing medium (ice-sodium chloride) cooling, and the mixture is stirred for 15 minutes. Then, a 40% aqueous N-methylamlne solution (0.756 ml) is added thereto under a freezing medium (ice-sodium chloride) cooling, and the mixture is further stirred for two hours. A 5% aqueous sodium hydrogencarbonate solution is added to the system of reaction, and the whole is extracted with ethyl acetate. The organic layer is washed with a saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The obtained residue is purified by silica gel column chromatography to give the titled compound.

Workup

  1. stirringthe mixture is further stirred for two hours
  2. extractionthe whole is extracted with ethyl acetate
  3. washThe organic layer is washed with a saturated sodium chloride solution
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe obtained residue is purified by silica gel column chromatography

Sources & evidence

ORD record
ord-bd20608c560c416da97a05934dce605e
Source dataset
uspto-grants-2000_04
Patent number
US06046235

Reaction notes

Loading…