Cyclobutylamine → 1-cyclobutyl-1H-imidazole-4-carboxylic acid ethyl ester

HRID 82303Notes

Reaction equation

HRID 82303 reaction equation
C[N:2]([CH3:12])[CH:3]=[C:4]([N+:10]#[C-:11])[C:5]([O:7][CH2:8][CH3:9])=[O:6].[CH:13]1(N)[CH2:16]C[CH2:14]1>>[CH2:8]([O:7][C:5]([C:4]1[N:10]=[CH:11][N:2]([CH:12]2[CH2:16][CH2:13][CH2:14]2)[CH:3]=1)=[O:6])[CH3:9]

Participants

3

Reactant 2

HCID 75645CyclobutylamineHCID 54355309Ethyl 3-(dimethylamino)-2-isocyanoacrylate

Product 1

HCID 866721321-cyclobutyl-1H-imidazole-4-carboxylic acid ethyl ester

Procedure

Ethyl 3-(dimethylamino)-2-isocyanoacrylate (WO 2007042545) (45 g, 0.27 mol) was added to cyclobutylamine (50 g, 0.70 mol) and heated to reflux for 2 hours. The solution was then cooled and concentrated. The residue was purified by column chromatography over silica gel (3:1 EtOAc:Heptane). The oily residue was triturated with TBME:heptane (1:1) and the resulting solid was collected and dried, giving 1-cyclobutyl-1H-imidazole-4-carboxylic acid ethyl ester (35 g, 67%, second crop not harvested). 1-Cyclobutyl-1H-imidazole-4-carboxylic acid ethyl ester (35 g, 0.21 mol) was dissolved in 6 N HCl (300 mL) and refluxed for 1 day. The solution was concentrated to dryness in vacuo. The solid was azeotroped with toluene, triturated with toluene and then dried under vacuum, giving the title compound 88% yield, 37.2 g, m/z 167 [M+H]+.

Workup

  1. temperatureheated
  2. temperatureto reflux for 2 hours
  3. temperatureThe solution was then cooled
  4. concentrationconcentrated
  5. customThe residue was purified by column chromatography over silica gel (3:1 EtOAc:Heptane)
  6. customThe oily residue was triturated with TBME:heptane (1:1)
  7. customthe resulting solid was collected
  8. customdried

Sources & evidence

ORD record
ord-e40430381a7b4ff6b47a715dea8249cc
Source dataset
uspto-grants-2014_09
Patent number
US08846698B2

Reaction notes

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