4-Methylmorpholine → 5-Benzyl 1-methyl N-(tert-butoxycarbonyl)-L-glutamate

HRID 1930780Notes

Reaction equation

HRID 1930780 reaction equation
[CH2:1]([O:8][C:9](=[O:24])[CH2:10][CH2:11][C@H:12]([NH:16][C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[C:13]([OH:15])=[O:14])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=C[C:35]=2N=N1.CN1CCOCC1.[OH-].[Na+]>C(#N)C.CO>[CH3:35][O:14][C:13](=[O:15])[C@@H:12]([NH:16][C:17]([O:19][C:20]([CH3:21])([CH3:23])[CH3:22])=[O:18])[CH2:11][CH2:10][C:9]([O:8][CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)=[O:24]

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 14798Sodium HydroxideHCID 83589L-Glutamic acid, N-((1,1-dimethylethoxy)carbonyl)-, 5-(phenylmethyl) esterHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate

Product 1

HCID 139430705-Benzyl 1-methyl N-(tert-butoxycarbonyl)-L-glutamateYield 121.5%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6342AcetonitrileSolvent

Procedure

To a mixture of (S)-2-tert-butoxycarbonylamino-pentanedioic acid 5-benzyl ester (300 mg, 0.89 mmol) and methanol (4 mL) were added benzotriazol-1-yloxytris-(dimethylamino)-phosphonium hexafluorophosphate (390 mg, 0.89 mmol), N-methylmorpholine (98 μL, 0.89 mmol), and acetonitrile (1 mL) at 0° C., which was stirred overnight at room temperature. A 1N sodium hydroxide aqueous solution was added to the reaction mixture, which was extracted with ethyl acetate. The organic layer was washed first with water and then with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under a reduced pressure, so as to obtain the titled compound (380 mg, purity of 66%) in a crude form.

Workup

  1. extractionwas extracted with ethyl acetate
  2. washThe organic layer was washed first with water
  3. dry with materialwith saturated brine, and dried over anhydrous magnesium sulfate
  4. customThe solvent was evaporated under a reduced pressure

Sources & evidence

ORD record
ord-5369542e27b74f1b98354cbe1a4302e6
Source dataset
uspto-grants-2012_05
Patent number
US08188119B2

Reaction notes

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