Sodium Hydroxide → HCID 178468836, compound

HRID 1194389Notes

Reaction equation

HRID 1194389 reaction equation
BrBr.[NH:3]1[CH:7]=[C:6]([CH2:8][CH:9]2[CH2:14][CH2:13][CH2:12][CH:11]([C:15]([O:17][CH2:18][CH3:19])=[O:16])[C:10]2=[O:20])[N:5]=[CH:4]1.[OH-].[Na+]>C(O)(=O)C>[NH:3]1[CH:7]=[C:6]([CH2:8][C:9]2[C:10]([OH:20])=[C:11]([CH:12]=[CH:13][CH:14]=2)[C:15]([O:17][CH2:18][CH3:19])=[O:16])[N:5]=[CH:4]1

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 24408BromineHCID 178468835HCID 178468835, compound

Product 1

HCID 178468836HCID 178468836, compoundYield 56%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent2×

Conditions

Temperature
20 °C

Procedure

176 g (56.5 ml; 1.1 mole) of bromine dissolved in 400 ml of glacial acetic acid are added dropwise within 30 minutes, at 17° to 20° C. and under an atmosphere of argon, to a solution containing 37.5 g (0.55 mole) of ethyl 3-[(1H-imidazol-4-yl)methyl]-2-oxo-cyclohexanecarboxylate in 1.5 liter of glacial acetic acid. The reaction mixture is subsequently heated under reflux for 4 hours. The red solution becomes progressively blacker. The mixture is cooled to 20° C. and evaporated under reduced pressure. The residue is taken up in 1.2 liter of 50% aqueous acetic acid. There are then added a spatula tip of anion exchange resin (Amberlite IR 45 acetate), 25 g of 10% palladium on carbon and 25 g of 10% rhodium on carbon and hydrogenolysis is carried out for 150 minutes under a hydrogen pressure of 3.5 bars. The reaction mixture is filtered on Celite and the filtrate is evaporated under reduced pressure. The oil obtained is dissolved in 1 liter of an ice-water mixture and the solution is adjusted to a pH of 8 by the addition of a 2N aqueous sodium hydroxide solution and rapidly extracted 5 times with 400 ml of ethyl acetate. The organic phases are combined, dried over anhydrous magnesium sulfate, filtered and evaporated under reduced pressure. The residue is purified by chromatography on silica (eluent: 93.5:6.0:0.5 v/v/v dichloromethane-ethanol-ammonia). There are obtained 75.9 g of ethyl 3-[(1H-imidazol-4-yl)methyl]-2-hydroxybenzoate in the form of an oil which crystallizes slowly. Yield: 55% of theory; M.P.: 133° C.

Workup

  1. additionare added dropwise within 30 minutes, at 17° to 20° C. and under an atmosphere of argon, to a solution
  2. temperatureThe reaction mixture is subsequently heated
  3. temperatureunder reflux for 4 hours
  4. customevaporated under reduced pressure
  5. additionThere are then added a spatula tip of anion exchange resin (Amberlite IR 45 acetate), 25 g of 10% palladium on carbon and 25 g of 10% rhodium on carbon and hydrogenolysis
  6. filtrationThe reaction mixture is filtered on Celite
  7. customthe filtrate is evaporated under reduced pressure
  8. customThe oil obtained
  9. extractionrapidly extracted 5 times with 400 ml of ethyl acetate
  10. dry with materialdried over anhydrous magnesium sulfate
  11. filtrationfiltered
  12. customevaporated under reduced pressure
  13. customThe residue is purified by chromatography on silica (eluent: 93.5:6.0:0.5 v/v/v dichloromethane-ethanol-ammonia)

Sources & evidence

ORD record
ord-bebec04adca842309e4a213ce26db271
Source dataset
uspto-grants-1989_03
Patent number
US04814343

Reaction notes

Loading…