Guanidine → tert-butyl (2S)-3-[4-(4-carbamimidamido-4-oxobutoxy)phenyl]-2-(phenylmethoxycarbonylamino)propanoate

HRID 2184947Notes

Reaction equation

HRID 2184947 reaction equation
[NH2:1][C:2]([NH2:4])=[NH:3].[CH2:5]([O:12][C:13]([NH:15][C@@H:16]([CH2:24][C:25]1[CH:30]=[CH:29][C:28]([O:31][CH2:32][CH2:33][CH2:34][C:35](OCC)=[O:36])=[CH:27][CH:26]=1)[C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])=[O:14])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1>C(O)(C)(C)C.C1COCC1>[CH2:5]([O:12][C:13]([NH:15][C@@H:16]([CH2:24][C:25]1[CH:30]=[CH:29][C:28]([O:31][CH2:32][CH2:33][CH2:34][C:35]([NH:3][C:2]([NH2:4])=[NH:1])=[O:36])=[CH:27][CH:26]=1)[C:17]([O:19][C:20]([CH3:22])([CH3:21])[CH3:23])=[O:18])=[O:14])[C:6]1[CH:7]=[CH:8][CH:9]=[CH:10][CH:11]=1

Participants

5

Reactant 2

HCID 3520Guanidine2×HCID 11038228tert-Butyl (2S)-2-benzyloxycarbonylamino-3-(4-(3-ethoxycarbonylpropyloxy)phenyl)propionate

Product 1

HCID 178451190tert-butyl (2S)-3-[4-(4-carbamimidamido-4-oxobutoxy)phenyl]-2-(phenylmethoxycarbonylamino)propanoateYield 42%

Reagents, catalysts & solvents 2

HCID 6386tert-ButanolSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 3.64 g (61.69 mmol) of guanidine in 150 ml of tert-butanol was added to a solution of 20 g (41.23 mmol) of (1.1) in THF and the mixture was stirred at room temperature for 18 h. A further 4.5 g of guanidine in 150 ml of tert-butanol were then added, and the reaction solution was stirred at room temperature for 7 h, concentrated to about a half and stirred at room temperature for a further 18 h. The solvent was removed in vacuo and the residue was first filtered through basic Al2O3 using CH2Cl2/MeOH/H2O (95/5/0.5) and then chromatographed on silica gel by means of MPLC using CH2Cl2/MeOH/acetic acid (90/10/0.5). 8.6 g (42%) of (1.2) were obtained.

Workup

  1. stirringthe reaction solution was stirred at room temperature for 7 h
  2. concentrationconcentrated to about a half
  3. stirringstirred at room temperature for a further 18 h
  4. customThe solvent was removed in vacuo
  5. filtrationthe residue was first filtered through basic Al2O3
  6. customchromatographed on silica gel by means of MPLC

Sources & evidence

ORD record
ord-54ccd8a338674e0ebc135f78d36cad75
Source dataset
uspto-grants-2002_06
Patent number
US06399620B1

Reaction notes

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