4-Methylmorpholine → N-[3-(ethoxycarbonyl)-2-(2-methylpropyl)propanoyl]-O-methyl-L-tyrosine N-methylamide

HRID 745618Notes

Reaction equation

HRID 745618 reaction equation
[CH2:1]([O:3][C:4]([CH2:6][CH:7]([CH2:11][CH:12]([CH3:14])[CH3:13])[C:8]([OH:10])=O)=[O:5])[CH3:2].CN1CCOCC1.C(Cl)(=O)C(Cl)=O.[CH3:28][NH:29][C:30](=[O:42])[C@H:31]([CH2:33][C:34]1[CH:39]=[CH:38][C:37]([O:40][CH3:41])=[CH:36][CH:35]=1)[NH2:32]>ClCCl.CN(C)C=O>[CH3:28][NH:29][C:30](=[O:42])[C@H:31]([CH2:33][C:34]1[CH:35]=[CH:36][C:37]([O:40][CH3:41])=[CH:38][CH:39]=1)[NH:32][C:8](=[O:10])[CH:7]([CH2:11][CH:12]([CH3:14])[CH3:13])[CH2:6][C:4]([O:3][CH2:1][CH3:2])=[O:5]

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 65578Oxalyl chlorideHCID 143030363-(Ethoxycarbonyl)-2-(2-methylpropyl)propanoic acidHCID 14303038O-methyl-L-tyrosine N-Methylamide

Product 1

HCID 14303040N-[3-(ethoxycarbonyl)-2-(2-methylpropyl)propanoyl]-O-methyl-L-tyrosine N-methylamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent3×

Conditions

Temperature
0 °C

Procedure

A mixture of 3-(ethoxycarbonyl)-2-(2-methylpropyl)propanoic acid (17.4 g., 0.087 mol.), N-methylmorpholine (28.7 mls., 0.26 mol.) and dimethylformamide (0.25 ml.) was dissolved in dry dichloromethane (200 mls.) and the resulting mixture was cooled to 0° C. To the reaction mixture was added a solution of oxalyl chloride (7.6 mls., 0.087 mol.) in dry dichloromethane (50 mls.). The mixture was heated under reflux for 10 minutes and then cooled to -70° C. To the reaction mixture was added O-methyl-L-tyrosine N-methylamide (20.0 g., 0.096 mol.) in dry dichloromethane (100 mls.) over a period of 30 minutes. The resulting mixture was allowed to warm to room temperature and stirred for 2.5 days. The mixture was filtered and the filtrate washed with saturated sodium bicarbonate solution (2×200 mls.), dilute citric acid (2×150 mls.) and then dried over anhydrous sodium sulfate. The solvent was then removed by evaporation in vacuo to yield N-[3-(ethoxycarbonyl)-2-(2-methylpropyl)propanoyl]-O-methyl-L-tyrosine N-methylamide, as a mixture of isomers (20.7 g.), in the form of a solid.

Workup

  1. temperatureThe mixture was heated
  2. temperatureunder reflux for 10 minutes
  3. temperaturecooled to -70° C
  4. temperatureto warm to room temperature
  5. filtrationThe mixture was filtered
  6. washthe filtrate washed with saturated sodium bicarbonate solution (2×200 mls.), dilute citric acid (2×150 mls.)
  7. dry with materialdried over anhydrous sodium sulfate
  8. customThe solvent was then removed by evaporation in vacuo

Sources & evidence

ORD record
ord-1e11f443478c4171bd3e16b20457b0b1
Source dataset
uspto-grants-1986_07
Patent number
US04599361

Reaction notes

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