Hydrochloric Acid → 1-Methyl-2-(thiophen-2-yl)-1H-imidazole

Temperature

85 °C

Methylaminoacetaldehyde dimethyl acetal (0.50 ml, 3.9 mmol), thiophene-2-carbonitrile (0.36 ml, 3.9 mmol) and copper(I) chloride (481 mg, 4.86 mmol) were combined in a sealed tube and heated to 85° C. for 12 hours. The mixture was allowed to reach ambient temperature, and methanol (2 ml) was added, followed with hydrochloric acid (4.8 M, 2.0 ml, 9.7 mmol). The resulting mixture was refluxed for 4 hours and concentrated under reduced pressure to remove methanol. The mixture was placed over an ice bath and 50% aqueous sodium hydroxide (1.24 g, 31.1 mmol) was added slowly to keep the temperature below 20° C. Then the mixture was diluted with ethyl acetate, stirred for 5 mins, filtered and washed with ethyl acetate. The filtrate was washed with brine, separated, dried over sodium sulfate, filtered and concentrated and taken forward without additional purification. LRMS (ESI) calculated for C8H9N2S [M+H]+, 165.0; found 165.1.

1. customto reach ambient temperature
2. temperatureThe resulting mixture was refluxed for 4 hours
3. concentrationconcentrated under reduced pressure
4. customto remove methanol
5. customThe mixture was placed over an ice bath
6. customthe temperature below 20° C
7. filtrationfiltered
8. washwashed with ethyl acetate
9. washThe filtrate was washed with brine
10. customseparated
11. dry with materialdried over sodium sulfate
12. filtrationfiltered
13. concentrationconcentrated
14. customtaken forward without additional purification

ORD record

ord-723ca45dde6b4b32808ce8f604baec33

Source dataset

uspto-grants-2013_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08455477B2