1,3-Dichloroacetone → 2-(Chloromethyl)-6-(trifluoromethyl)imidazo[1,2-a]pyridine

A mixture of 2-amino-5-trifluoromethylpyridine (Fluorochem; 3.19 g), 1,3-dichloroacetone (Aldrich; 3.00 g), and dimethoxyethane (Aldrich; 15 mL) is stirred at room temperature for 4 days. The resulting solid is collected and washed with several milliliters of dimethoxyethane. The solid is then taken up in ethanol (30 mL) and the mixture is heated at 80° C. for 2.5 h, at which time diisopropylethylamine (Aldrich; 3.5 mL) is added. After stirring with heating an additional 3.5 h, the mixture is cooled and the solvent is removed under reduced pressure. The residue is partitioned between dichloromethane and aq. sodium bicarbonate. The organic layers are filtered through sodium sulfate and concentrated; the residue is chromatographed on silica gel using methanol/dichloromethane (1/99) to give 3.33 g of 2-(chloromethyl)-6-(trifluoromethyl)imidazo[1,2-a]pyridine. 1H NMR (CDCl3) δ 4.78, 7.36, 7.69, 7.73, 8.48.

1. customThe resulting solid is collected
2. washwashed with several milliliters of dimethoxyethane
3. temperaturethe mixture is heated at 80° C. for 2.5 h, at which time diisopropylethylamine (Aldrich; 3.5 mL)
4. additionis added
5. stirringAfter stirring
6. temperaturewith heating an additional 3.5 h
7. temperaturethe mixture is cooled
8. customthe solvent is removed under reduced pressure
9. customThe residue is partitioned between dichloromethane and aq. sodium bicarbonate
10. filtrationThe organic layers are filtered through sodium sulfate
11. concentrationconcentrated
12. customthe residue is chromatographed on silica gel

ORD record

ord-c0032b047d9b4bb4bfb4499a15166263

Source dataset

uspto-grants-2000_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06013654