Sodium Iodide → 2-Amino-4-(3-methoxycarbonyl-propyl)-imidazole-1-carboxylic acid tert-butyl ester

HRID 242354Notes

Reaction equation

HRID 242354 reaction equation
[CH3:1][O:2][C:3](=[O:11])[CH2:4][CH2:5][CH2:6][C:7](=O)[CH2:8]Br.[C:12]([NH:19][C:20]([NH2:22])=[NH:21])([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13].[Na+].[I-]>CN(C=O)C>[C:15]([O:14][C:12]([N:19]1[CH:8]=[C:7]([CH2:6][CH2:5][CH2:4][C:3]([O:2][CH3:1])=[O:11])[N:21]=[C:20]1[NH2:22])=[O:13])([CH3:18])([CH3:16])[CH3:17]

Participants

5

Reactant 3

HCID 5238Sodium IodideHCID 582216Methyl 6-bromo-5-oxohexanoateHCID 178454308HCID 178454308, compound

Product 1

HCID 597660822-Amino-4-(3-methoxycarbonyl-propyl)-imidazole-1-carboxylic acid tert-butyl esterYield 65%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

6-bromo-5-oxo-hexanoic acid methyl ester (2.30 g, 10.3 mmol), Boc-guanidine (4.92 g, 30.9 mmol),32 and NaI (3.07 g, 20.6 mmol) were dissolved in DMF (30 mL) and allowed to stir at room temperature. After 24 h the DMF was removed under reduced pressure and the residue was taken up in ethyl acetate (100 mL) and washed with water (3×50 mL) and brine (50 mL) before being dried (Na2SO4), filtered and evaporated to dryness. The resulting oil was purified by flash column chromatography (50-100% EtOAc/Hexanes) to obtain a yellow oil. Trituration of the viscous oil with cold hexanes (20 mL) produced a precipitate, which upon filtration yielded 18 (1.89 g, 65%) as a pale yellow solid. 1H NMR (400 MHz, CDCl3) δ 6.53 (s, 1H), 5.6 (br s, 2H), 2.41 (t, 2H, J=7.2 Hz), 2.37 (t, 2H, J=7.2 Hz), 1.93 (quint., 2H, J=7.2 Hz), 1.58 (s, 9H); 13C NMR (75 MHz, CDCl3) δ 174.09, 150.11, 149.61, 138.39, 107.15, 84.81, 51.56, 33.65, 28.18, 27.68, 23.82; HRMS (ESI) calcd for C13H22N3O4 (MH)+284.1604, found 284.1606.

Workup

  1. customAfter 24 h the DMF was removed under reduced pressure
  2. washwashed with water (3×50 mL) and brine (50 mL)
  3. dry with materialbefore being dried (Na2SO4)
  4. filtrationfiltered
  5. customevaporated to dryness
  6. customThe resulting oil was purified by flash column chromatography (50-100% EtOAc/Hexanes)
  7. customto obtain a yellow oil
  8. filtrationupon filtration

Sources & evidence

ORD record
ord-08b17c3dcdf2492393ba8e02a024a7c3
Source dataset
uspto-grants-2014_02
Patent number
US08653124B2

Reaction notes

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