1-Methylimidazole → 4-(3-methyl-3H-imidazol-4-yl)-benzoic acid methyl ester

HRID 1593981Notes

Reaction equation

HRID 1593981 reaction equation
C([O-])([O-])=O.[Cs+].[Cs+].[CH3:7][N:8]1[CH:12]=[CH:11][N:10]=[CH:9]1.[CH3:13][O:14][C:15](=[O:23])[C:16]1[CH:21]=[CH:20][C:19](I)=[CH:18][CH:17]=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[OH-].[Na+]>CC([O-])=O.CC([O-])=O.[Pd+2].CN(C)C=O>[CH3:13][O:14][C:15](=[O:23])[C:16]1[CH:21]=[CH:20][C:19]([C:12]2[N:8]([CH3:7])[CH:9]=[N:10][CH:11]=2)=[CH:18][CH:17]=1

Participants

8

Reactant 5

HCID 13901-MethylimidazoleHCID 10796Cesium carbonateHCID 11776TriphenylphosphineHCID 14798Sodium HydroxideHCID 69273Methyl 4-iodobenzoate

Product 1

HCID 113333954-(3-methyl-3H-imidazol-4-yl)-benzoic acid methyl esterYield 38.5%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Procedure

4-(3-Methyl-3H-imidazol-4-yl)-benzoic acid methyl ester was prepared using the procedure similar to that outlined by Pivsa-Art, S.,; Satoh, T., Kawamura, Y., Miura, M., Nomura, M. Bull. Chem. Soc. Jpn. 71, 1998, 467. In a flask was dried Cs2CO3 (3.29 g, 12 mmol) in vacuo at 150° C. for 1.5 hr. After cooling to ambient temperature, N-methylimidazole (0.5 mL, 6 mmol), methyl-4-iodo-benzoate (3.29 g, 12 mmmol), Pd(OAc)2 (0.14 g, 0.6 mmol), PPh3 (4.09 g, 12 mmol), and 20 mL dimethylformamide. The mixture was stirred under nitrogen at 140° C. for 24 hrs and an additional 16 hrs at ambient temperature. The mixture was poured onto 10% aqueous NaOH and extracted with CH2Cl2, dried over Na2SO4. Purification by chromatography (5% MeOH/CHCl3) gave 0.50 g (37%) of 4-(3-methyl-3H-imidazol-4-yl)-benzoic acid methyl ester. A solution of 4-(3-methyl-3H-imidazol-4-yl)-benzoic acid methyl ester (216 mg, 1 mmol), lithium hydroxide (44.0 mg, 1 mmol), tetrahydrofuran (0.6 mL), water (0.6 mL), and methanol (0.6 mL) was stirred at ambient temperature under nitrogen for 24 hrs. The mixture was concentrated in vacuo and then lyophilized to give 242 g of crude material which was taken on without further purification for preparation of compound 42 of Table 1.

Workup

  1. custom4-(3-Methyl-3H-imidazol-4-yl)-benzoic acid methyl ester was prepared
  2. customIn a flask was dried
  3. extractionextracted with CH2Cl2
  4. dry with materialdried over Na2SO4
  5. customPurification by chromatography (5% MeOH/CHCl3)

Sources & evidence

ORD record
ord-b1a68a63b7844efbac00bec7c67094d3
Source dataset
uspto-grants-2007_11
Patent number
US07300934B2

Reaction notes

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