Sodium Carbonate → 3-(4-Chloro-phenyl)-5-(2-methyl-imidazol-1-yl-methyl)-pyridine Hydrochloride

HRID 433569Notes

Reaction equation

HRID 433569 reaction equation
Br[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([CH2:8][N:9]2[CH:13]=[CH:12][N:11]=[C:10]2[CH3:14])[CH:7]=1.CC([O-])=O.[K+].[Cl:20][C:21]1[CH:26]=[CH:25][C:24](B(O)O)=[CH:23][CH:22]=1.C([O-])([O-])=O.[Na+].[Na+].Cl.CCO>O1CCOCC1.C1(C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)[Pd][P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[ClH:20].[Cl:20][C:21]1[CH:26]=[CH:25][C:24]([C:2]2[CH:3]=[N:4][CH:5]=[C:6]([CH2:8][N:9]3[CH:13]=[CH:12][N:11]=[C:10]3[CH3:14])[CH:7]=2)=[CH:23][CH:22]=1

Participants

8

Reactant 5

HCID 10340Sodium CarbonateHCID 742994-Chlorophenylboronic acidHCID 517044Potassium AcetateHCID 21887872Ethanol hydrochlorideHCID 234449653-Bromo-5-(2-methyl-imidazol-1-ylmethyl)-pyridine

Product 1

HCID 234451403-(4-Chloro-phenyl)-5-(2-methyl-imidazol-1-yl-methyl)-pyridine HydrochlorideYield 1,224.2%

Reagents, catalysts & solvents 2

HCID 178419050HCID 178419050, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 3-bromo-5-(2-methyl-imidazol-1-ylmethyl)-pyridine (120 mg, 0.48 mmol), bis(triphenylphosphine)palladium (II) choride (10 mg, 0.01 mmol) and KOAc (140 mg, 0.14 mmol) were stirred in dioxane (10 ml) for 1 h at 20° C. 4-Chlorophenyl boronic acid (78 mg, 0.05 mmol) and 2N Na2CO3 solution (1.2 ml) were then added and the mixture heated to 100° C. for 7-24 h under an argon atmosphere. After cooling, the solvent was evaporated and 2N NaOH (5 ml) and AcOEt were added. The mixture was shaken and the aqueous phase separated and further extracted with AcOEt, the combined organic extracts were washed with brine then dried over Na2SO4, filtered and evaporated. The residue was chromatographed [silica, elution with CH2Cl2/(2M NH3 in MeOH)=97:3)]. The product was dissolved in MeOH, cooled to 4° C. with stirring and treated with HCl/EtOH (1.46 M 1.1 eq) for 45 min. Evaporation of the solvent and drying under high vacuum at 50° C. for 2 h afforded the title compound (98 mg, 64%) as a light brown solid. MS: m/e=284.2 (M+H+).

Workup

  1. temperatureAfter cooling
  2. customthe solvent was evaporated
  3. addition2N NaOH (5 ml) and AcOEt were added
  4. customthe aqueous phase separated
  5. extractionfurther extracted with AcOEt
  6. washthe combined organic extracts were washed with brine
  7. dry with materialthen dried over Na2SO4
  8. filtrationfiltered
  9. customevaporated
  10. customThe residue was chromatographed [
  11. washsilica, elution with CH2Cl2/(2M NH3 in MeOH)=97:3)]
  12. dissolutionThe product was dissolved in MeOH
  13. temperaturecooled to 4° C.
  14. stirringwith stirring
  15. customEvaporation of the solvent
  16. customdrying under high vacuum at 50° C. for 2 h

Sources & evidence

ORD record
ord-1260873c8b4640f0848f6abec7c6bf93
Source dataset
uspto-grants-2003_12
Patent number
US06667335B2

Reaction notes

Loading…