6-Bromo-5-oxo-hexanoic acid benzyl ester → 2-Amino-4-(3-benzyloxycarbonyl-propyl)-imidazole-1-carboxylic acid tert-butyl ester

HRID 242355Notes

Reaction equation

HRID 242355 reaction equation
[CH2:1]([O:8][C:9](=[O:17])[CH2:10][CH2:11][CH2:12][C:13](=O)[CH2:14]Br)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:18]([NH:25][C:26]([NH2:28])=[NH:27])([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19]>CN(C=O)C>[C:21]([O:20][C:18]([N:25]1[CH:14]=[C:13]([CH2:12][CH2:11][CH2:10][C:9]([O:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[O:17])[N:27]=[C:26]1[NH2:28])=[O:19])([CH3:24])([CH3:22])[CH3:23]

Participants

4

Reactant 2

HCID 866217906-Bromo-5-oxo-hexanoic acid benzyl esterHCID 178454308HCID 178454308, compound

Product 1

HCID 670619352-Amino-4-(3-benzyloxycarbonyl-propyl)-imidazole-1-carboxylic acid tert-butyl esterYield 66%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

6-bromo-5-oxo-hexanoic acid benzyl ester (3.42 g, 11.99 mmol) and Boc-guanidine (5.73 g, 35.97 mmol) were dissolved in DMF (35 mL) and allowed to stir at room temperature. After 48 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 (30-100% EtOAc/Hexanes) to obtain the title compound (2.79 g, 66%) as a colorless oil which solidified upon prolonged standing. 1H NMR (400 MHz, CDCl3) δ 7.35 (m, 5H), 6.51 (s, 1H), 5.91 (s, 2H), 5.12 (s, 2H), 2.41 (m, 4H), 1.94 (quint., 2H, J=7.2 Hz), 1.57 (s, 9H); 13C NMR (75 MHz, CDCl3) δ 173.45, 150.31, 149.59, 138.27, 136.36, 128.67, 128.29, 128.27, 107.05, 84.73, 66.23, 33.82, 28.16, 27.62, 23.79; HRMS (ESI) calcd for C19H26N3O4 (MH)+360.1917, found 360.1919.

Workup

  1. customAfter 48 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 (30-100% EtOAc/Hexanes)

Sources & evidence

ORD record
ord-743644637ede4023968e7ce3817c07bf
Source dataset
uspto-grants-2014_02
Patent number
US08653124B2

Reaction notes

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