Pyridine → N-[(1,1-Dimethylethoxy)carbonyl]-1-phenyl-L-histidine methyl ester

HRID 497570Notes

Reaction equation

HRID 497570 reaction equation
[C:1]1(B(O)O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.N1C=CC=CC=1.[C:16]([O:20][C:21]([NH:23][C@@H:24]([CH2:29][C:30]1[N:31]=[CH:32][NH:33][CH:34]=1)[C:25]([O:27][CH3:28])=[O:26])=[O:22])([CH3:19])([CH3:18])[CH3:17].C(N(CC(O)=O)CC(O)=O)CN(CC(O)=O)CC(O)=O>ClCCl.C(=O)(O)[O-].[Na+].C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[C:16]([O:20][C:21]([NH:23][C@@H:24]([CH2:29][C:30]1[N:31]=[CH:32][N:33]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[CH:34]=1)[C:25]([O:27][CH3:28])=[O:26])=[O:22])([CH3:19])([CH3:17])[CH3:18]

Participants

8

Reactant 4

HCID 1049PyridineHCID 6049Ethylenediaminetetraacetic AcidHCID 66827Phenylboronic AcidHCID 178501431HCID 178501431, compound

Product 1

HCID 60030591N-[(1,1-Dimethylethoxy)carbonyl]-1-phenyl-L-histidine methyl esterYield 52%

Reagents, catalysts & solvents 3

HCID 8895Cupric acetateCatalystHCID 6344DichloromethaneSolventHCID 516892Sodium BicarbonateSolvent

Procedure

Phenylboronic acid (2.44 g, 20 mmol), copper acetate (2.72 g, 15 mmol), 4 Å molecular sieves (3 g) and pyridine (1.62 ml, 20 mmol) were added to a solution of methyl (2S)-2-[(tert-butoxycarbonyl)amino]-3-(1H-imidazol-4-yl)propanoate (2.69 g, 10 mmol) in dichloromethane (60 ml), and the reaction mixture stirred at room temperature whilst bubbling through compressed air, for 2 days. A solution of ethylenediaminetetraacetic acid (5 g, 17 mmol) in saturated sodium bicarbonate solution (200 ml) was added and the mixture stirred at room temperature for 20 minutes. The phases were separated, the aqueous layer extracted with dichloromethane (2×100 ml), and the combined organic extracts dried (MgSO4), filtered, and concentrated under reduced pressure. The residue was azeotroped with toluene (300 ml), and then purified by column chromatography on silica gel using an elution gradient of pentane:ethyl acetate (100:0 to 40:60), to afford the title compound as a yellow gum, 1.87 g, 52% yield.

Workup

  1. customwhilst bubbling through compressed air, for 2 days
  2. stirringthe mixture stirred at room temperature for 20 minutes
  3. customThe phases were separated
  4. extractionthe aqueous layer extracted with dichloromethane (2×100 ml)
  5. dry with materialthe combined organic extracts dried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was azeotroped with toluene (300 ml)
  9. custompurified by column chromatography on silica gel using an elution gradient of pentane:ethyl acetate (100:0 to 40:60)

Sources & evidence

ORD record
ord-effd9fbdadc14b7093404a962810075e
Source dataset
uspto-grants-2005_09
Patent number
US06949577B2

Reaction notes

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