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

HRID 497570노트

반응식

HRID 497570 반응식
[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]

참가 물질

8

반응물 4

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

생성물 1

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

시약·촉매·용매 3

HCID 8895Cupric acetate촉매HCID 6344Dichloromethane용매HCID 516892Sodium Bicarbonate용매

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-effd9fbdadc14b7093404a962810075e
출처 데이터셋
uspto-grants-2005_09
특허 번호
US06949577B2

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