4-Cyanobenzaldehyde → 2-bromo-5-[(4-cyano-phenyl)-hydroxy-methyl]-1-isopropyl-1H-imidazole-4-carboxylic acid ethyl ester

HRID 2410100Notes

Reaction equation

HRID 2410100 reaction equation
[Li+].CC([N-]C(C)C)C.[CH2:9]([O:11][C:12]([C:14]1[N:15]=[C:16]([Br:22])[N:17]([CH:19]([CH3:21])[CH3:20])[CH:18]=1)=[O:13])[CH3:10].[C:23]([C:25]1[CH:32]=[CH:31][C:28]([CH:29]=[O:30])=[CH:27][CH:26]=1)#[N:24]>C1COCC1>[CH2:9]([O:11][C:12]([C:14]1[N:15]=[C:16]([Br:22])[N:17]([CH:19]([CH3:21])[CH3:20])[C:18]=1[CH:29]([C:28]1[CH:31]=[CH:32][C:25]([C:23]#[N:24])=[CH:26][CH:27]=1)[OH:30])=[O:13])[CH3:10]

Participants

5

Reactant 3

HCID 660424-CyanobenzaldehydeHCID 2724682Lithium diisopropylamideHCID 86707750ethyl 2-bromo-1-isopropyl-1H-imidazole-4-carboxylate

Product 1

HCID 867077572-bromo-5-[(4-cyano-phenyl)-hydroxy-methyl]-1-isopropyl-1H-imidazole-4-carboxylic acid ethyl esterYield 66.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-70 °C

Procedure

LDA (2 M in THF, 53.6 mL, 107 mmol) was added slowly (over 30 min) to a cold (−78° C.) solution of intermediate A (20 g, 77 mmol) in THF (400 mL) (during the addition, the temperature raised to −70° C.). The mixture was stirred for 1 h at −78° C. A solution of 4-cyanobenzaldehyde (14 g, 107 mmol) in THF (100 mL) was added slowly. The reaction mixture was stirred for 30 min at −78° C., allowed to warm to −20° C. over 1 h, quenched by addition of acetic acid (10 mL), diluted with EtOAc/water, and extracted with EtOAc. The organic extracts were washed with water and brine, dried (Na2SO4), filtered, and concentrated. The residue was purified by flash chromatography (hexane/EtOAc, 1:1), followed by trituration in EtOAc, to provide 20.1 g of the title compound. tR: 0.99 min (LC-MS 2); ESI-MS: 392.2/394.1 [M+H]+ (LC-MS 2); Rf=0.29 (hexane/EtOAc, 1:1).

Workup

  1. additionduring the addition
  2. stirringThe reaction mixture was stirred for 30 min at −78° C.
  3. temperatureto warm to −20° C. over 1 h
  4. customquenched by addition of acetic acid (10 mL)
  5. additiondiluted with EtOAc/water
  6. extractionextracted with EtOAc
  7. washThe organic extracts were washed with water and brine
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe residue was purified by flash chromatography (hexane/EtOAc, 1:1)

Sources & evidence

ORD record
ord-cc1a96d864454b7484359d1166658e88
Source dataset
uspto-grants-2014_08
Patent number
US08815926B2

Reaction notes

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