4-Methylmorpholine → HCID 13072333, compound

HRID 1742749Notes

Reaction equation

HRID 1742749 reaction equation
[NH:1]([C:14]([O:16][CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)=[O:15])[C@H:2]([C:11]([OH:13])=O)[CH2:3][C:4](=[O:10])[O:5][C:6]([CH3:9])([CH3:8])[CH3:7].CN1CCOCC1.C(OC(Cl)=O)C(C)C.[NH2:39][C@H:40]([C:48]([NH2:50])=[O:49])[CH2:41][C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1>C1COCC1.CN(C=O)C.O.C(OCC)(=O)C>[NH:1]([C:14]([O:16][CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)=[O:15])[C@H:2]([C:11]([NH:39][C@H:40]([C:48]([NH2:50])=[O:49])[CH2:41][C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1)=[O:13])[CH2:3][C:4](=[O:10])[O:5][C:6]([CH3:7])([CH3:8])[CH3:9]

Participants

9

Reactant 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 1110824-tert-Butyl hydrogen N-((phenylmethoxy)carbonyl)-L-aspartateHCID 445694Phenylalanine amide

Product 1

HCID 13072333HCID 13072333, compoundYield 89.2%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a -10° C. solution of Cbz-Asp(O-t-Bu) (2.5 g, 4.95 mmol) in THF (40 mL) were added NMM (0.52 g, 5.18 mmol) followed by isobutylchloroformate (0.705 g, 5.16 mmol) to form a white precipitate. The suspension was stirred for 4 minutes and a solution of Phe-NH2 (0.81 g, 4.94 mmol) in DMF (10 mL) and water (5 mL) were added. The solution was stirred at -15° C. for additional 10 minutes then allowed to warm to ambient temperature. After 6 hours, the solution was diluted with ethyl acetate, washed with 1M HCl, saturated bicarbonate solution and brine. After drying over anhydrous sodium sulfate, the solvent was removed in vacuo to yield 2.07 g (89% yield) of the title compound as a white solid which was recrystallied from ethyl acetate. MS(FAB+) m/e 470 (M+H+). 1H NMR (300 MHz,CDCl3) δ1.41 (s, 9H), 2.67 (dd, J=6 and 15 Hz, 1H), 2.80 (dd, 1H), 3.03-3.22 (m, 2H), 4.42 (m, 2H), 4.64 (m, 2H), 5.17 (dd, 2H), 7.15-7.40 (m, 10H).

Workup

  1. customto form a white precipitate
  2. stirringThe solution was stirred at -15° C. for additional 10 minutes
  3. waitAfter 6 hours
  4. washwashed with 1M HCl, saturated bicarbonate solution and brine
  5. dry with materialAfter drying over anhydrous sodium sulfate
  6. customthe solvent was removed in vacuo

Sources & evidence

ORD record
ord-528b93b8fbdb48a29418daf23353dca8
Source dataset
uspto-grants-1994_08
Patent number
US05340802

Reaction notes

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