Dimethylformamide → 5-(4-fluorophenyl)4-(4-methylthiophenyl)-1H-imidazole-2-carboxaldehyde

Temperature

-70 °C

A solution of the compound from step 2 (500 mg, 1.4 mmol) and tetramethylethylenediamine (TMEDA) (186 mg, 1.6 mmol) in tetrahydrofuran (8 ml) was cooled to −70° C. under an argon atmosphere. n-Butyllithium (1.2 ml of 1.6M solution in hexane, 1.9 mmol) was added and the solution stirred at −70° C. for 15 minutes. Dimethylformamide (DMF) (140 mg, 1.9 mmol) was added and the solution was warmed to 0° C. The reaction was quenched by the addition of saturated NaHCO3 solution (2 ml) and extracted with diethyl ether. The organic phase was separated and dried (Na2SO4). The drying agent was filtered and the filtrate concentrated in vacuo. The residue was treated with 2N HCl (5 ml) in EtOH (10 ml) at room temperature for 24 hours. The reaction solution was made basic with NaHCO3, diluted with water (20 ml) and extracted with methylene chloride. After evaporation, the residue was purified by chromatography on silica gel, eluting with toluene/methanol (90/10), to give 350 mg (70%) of titled compound which was used immediately without further purification.

1. temperaturethe solution was warmed to 0° C
2. customThe reaction was quenched by the addition of saturated NaHCO3 solution (2 ml)
3. extractionextracted with diethyl ether
4. customThe organic phase was separated
5. dry with materialdried (Na2SO4)
6. filtrationThe drying agent was filtered
7. concentrationthe filtrate concentrated in vacuo
8. additionThe residue was treated with 2N HCl (5 ml) in EtOH (10 ml) at room temperature for 24 hours
9. additiondiluted with water (20 ml)
10. extractionextracted with methylene chloride
11. customAfter evaporation
12. customthe residue was purified by chromatography on silica gel
13. washeluting with toluene/methanol (90/10)

ORD record

ord-b74b4bf0129c4afa93b327c21cd06486

Source dataset

uspto-grants-2002_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06426360B1