Dicyclohexylcarbodiimide → HCID 178501424, compound

HRID 979657Notes

Reaction equation

HRID 979657 reaction equation
Cl.Cl.[CH3:3][O:4][C:5](=[O:14])[C@H:6]([CH2:8][C:9]1[N:13]=[CH:12][NH:11][CH:10]=1)[NH2:7].[C:15]([NH:22][C@H:23]([C:31](O)=[O:32])[CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16].ON1C2C=CC=CC=2N=N1.C1(N=C=NC2CCCCC2)CCCCC1>ClCCl.C(N(CC)CC)C>[CH3:3][O:4][C:5](=[O:14])[C@H:6]([CH2:8][C:9]1[N:13]=[CH:12][NH:11][CH:10]=1)[NH:7][C:31](=[O:32])[C@H:23]([CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[NH:22][C:15]([O:17][C:18]([CH3:21])([CH3:19])[CH3:20])=[O:16]

Participants

7

Reactant 4

HCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 77857L-Phenylalanine, N-[(1,1-dimethylethoxy)carbonyl]-HCID 178419105HCID 178419105, compound

Product 1

HCID 178501424HCID 178501424, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
20 °C

Procedure

A slurry of 36.4 g. L-histidine methyl ester dihydrochloride in dichloromethane (1 l.) was cooled to 5° C. and treated with 52 ml. triethylamine. After 10 minutes 40 g. Boc-L-phenylalanine was added followed by 1-hydroxybenzotriazole (30.6 g.), then after another 5 minutes by dicyclohexylcarbodiimide (30.8 g.), and the mixture was stirred at 0° C. for 4 hours and at 20° C. for 90 hours. The mixture was then filtered and the filtered solid was washed with dichloromethane, and the combined organic layers were concentrated and the residue was dissolved in 1 l. ethyl acetate. After 10 minutes of stirring the mixture was filtered and the filtrate was washed with 1N sodium hydroxide (3×150 ml.), brine, dried over magnesium sulfate and concentrated giving 45.9 g. of a colorless solid which was used without additional purification in Step B.

Workup

  1. additiontreated with 52 ml
  2. filtrationThe mixture was then filtered
  3. washthe filtered solid was washed with dichloromethane
  4. concentrationthe combined organic layers were concentrated
  5. dissolutionthe residue was dissolved in 1 l
  6. stirringAfter 10 minutes of stirring the mixture
  7. filtrationwas filtered
  8. washthe filtrate was washed with 1N sodium hydroxide (3×150 ml.), brine
  9. dry with materialdried over magnesium sulfate
  10. concentrationconcentrated
  11. customgiving 45.9 g
  12. customof a colorless solid which was used without additional purification in Step B

Sources & evidence

ORD record
ord-7ea6848946684247bd468856e10b7bfc
Source dataset
uspto-grants-1987_05
Patent number
US04668769

Reaction notes

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