Triethylamine → HCID 178428962, compound

4-Imidazolecarboxylic acid (2 grams, 17.9 mmol) and thionyl chloride (5 mL, 68.5 mmol) were heated to reflux in anhydrous acetonitrile (50 mL) under nitrogen for 1 hour. Then all volatile was removed under vacuum. The conversion to acid chloride is almost quantitative. To a solution of imidazole acid chloride in anhydrous acetonitrile (10 mL) was added dropwise a solution of 2-amino-2-methyl-1-propanol) (2.1 g, 21.4 mmol) and triethylamine (3.0 mL, 21.4 mmol) in anhydrous acetonitrile (10 mL) at 0° C. under N2. After the addition, the ice-bath was removed and the mixture was stirred at room temperature for 5 hours. The white solid of triethylamine hydrochloride was filtered out. Solvent and excess aminoalcohol were removed under vacuum. Dark brown oil was obtained. The dark brown oil was dissolved in hot acetonitrile (20 mL). After the solution was cooled down, a solution of thionyl chloride (5 mL) in anhydrous acetonitrile (10 mL) was added dropwise at 0° C. After stirring at room temperature for 2 hours, all volatile was removed under vacuum. To the oily residue was added acetonitrile (20 mL) and 10% aqueous potassium carbonate solution (20 mL). The mixture was heated to reflux for 2 hours. Two layers were observed after the mixture was cooled down. The water layer was discarded. Sodium bicarbonate solution was added to the organic layer, and the resulting mixture was extracted with ethyl acetate 3 times. After drying over magnesium sulfate and removal of solvent, flash chromatography (ethyl acetate:methanol=4:1) yielded pure 2-(imidazol-4-yl)-4,4-dimethyloxazoline as brown oil (1.75 g, 60%). 1H NMR (acetone-d6) δ1.35 (s, 6H), 4.10 (s, 2H), 7.58(s, 1H), 7.85(s, 1H).

1. customThen all volatile was removed under vacuum
2. additionAfter the addition
3. customthe ice-bath was removed
4. filtrationThe white solid of triethylamine hydrochloride was filtered out
5. customSolvent and excess aminoalcohol were removed under vacuum
6. customDark brown oil was obtained
7. temperatureAfter the solution was cooled down
8. stirringAfter stirring at room temperature for 2 hours
9. customall volatile was removed under vacuum
10. additionTo the oily residue was added acetonitrile (20 mL) and 10% aqueous potassium carbonate solution (20 mL)
11. temperatureThe mixture was heated
12. temperatureto reflux for 2 hours
13. temperaturewas cooled down
14. additionSodium bicarbonate solution was added to the organic layer
15. extractionthe resulting mixture was extracted with ethyl acetate 3 times
16. dry with materialAfter drying over magnesium sulfate and removal of solvent, flash chromatography (ethyl acetate:methanol=4:1)

ORD record

ord-63cb2647c2154dcfbd4106bfc0e6c497

Source dataset

uspto-grants-2004_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06743919B2