Dicyclohexylcarbodiimide → N-[3-(ethoxycarbonyl)-2-(2-methylpropyl)butanoyl]-O-methyl-L-tyrosine N-methylamide

HRID 745625Notes

Reaction equation

HRID 745625 reaction equation
[CH2:1]([O:3][C:4]([CH:6]([CH3:15])[CH:7]([CH2:11][CH:12]([CH3:14])[CH3:13])[C:8]([OH:10])=O)=[O:5])[CH3:2].C1(N=C=NC2CCCCC2)CCCCC1.[CH3:31][NH:32][C:33](=[O:45])[C@H:34]([CH2:36][C:37]1[CH:42]=[CH:41][C:40]([O:43][CH3:44])=[CH:39][CH:38]=1)[NH2:35].C(=O)(O)[O-].[Na+]>ClCCl>[CH3:31][NH:32][C:33](=[O:45])[C@H:34]([CH2:36][C:37]1[CH:38]=[CH:39][C:40]([O:43][CH3:44])=[CH:41][CH:42]=1)[NH:35][C:8](=[O:10])[CH:7]([CH2:11][CH:12]([CH3:14])[CH3:13])[CH:6]([C:4]([O:3][CH2:1][CH3:2])=[O:5])[CH3:15]

Participants

6

Reactant 4

HCID 10868DicyclohexylcarbodiimideHCID 516892Sodium BicarbonateHCID 14303038O-methyl-L-tyrosine N-MethylamideHCID 199634113-(Ethoxycarbonyl)-2-(2-methylpropyl)butanoic acid

Product 1

HCID 54114084N-[3-(ethoxycarbonyl)-2-(2-methylpropyl)butanoyl]-O-methyl-L-tyrosine N-methylamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Conditions

Temperature
0 °C

Procedure

A mixture of 3-(ethoxycarbonyl)-2-(2-methylpropyl)butanoic acid (7.5 g., 0.037 mol.) and dichloromethane (70 mls.) was stirred and cooled to 0° C. To the mixture was added dropwise a solution of N,N'-dicyclohexylcarbodiimide (7.6 g., 0.37 mol.) in dichloromethane (20 mls.) and the reaction mixture was allowed to warm to room temperature. A solution of O-methyl-L-tyrosine N-methylamide (7.7 g., 0.037 mol.) in dichloromethane (45 mls.) was added to the reaction mixture and the resulting mixture was stirred overnight at room temperature. A saturated sodium bicarbonate solution (100 mls.) was added to the reaction mixture and the resulting mixture was stirred for an additional hour. The reaction mixture was filtered and the organic layer recovered and then dried on anhydrous sodium sulfate. The solvent was removed by evaporation in vacuo to yield a sticky brown solid. The solid was purified by chromatography on normal phase silica eluting with 20% hexane in ethyl acetate to yield N-[3-(ethoxycarbonyl)-2-(2-methylpropyl)butanoyl]-O-methyl-L-tyrosine N-methylamide as a mixture of 4 diastereomers.

Workup

  1. temperatureto warm to room temperature
  2. stirringthe resulting mixture was stirred overnight at room temperature
  3. stirringthe resulting mixture was stirred for an additional hour
  4. filtrationThe reaction mixture was filtered
  5. customthe organic layer recovered
  6. dry with materialdried on anhydrous sodium sulfate
  7. customThe solvent was removed by evaporation in vacuo
  8. customto yield a sticky brown solid
  9. customThe solid was purified by chromatography on normal phase silica eluting with 20% hexane in ethyl acetate

Sources & evidence

ORD record
ord-c1ebe605629b4d7e9ce890b6439fe495
Source dataset
uspto-grants-1986_07
Patent number
US04599361

Reaction notes

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