Sodium hydride → methyl 2-(4-(trifluoromethyl)-1H-imidazol-1-yl)acetate

Temperature

0 °C

To a solution of 4-(trifluoromethyl)-1H-imidazole (10.0 g, 73.5 mmol) in THF (75 mL) at 0° C. was added sodium hydride (60% in mineral oil, 3.25 g, 80.8 mmol) under nitrogen. The mixture was stirred at 0° C. for 30 min. Methyl bromoacetate (1.67 mL, 17.6 mmol) was added and the reaction was stirred for 3 h at room temperature. LC-MS showed the reaction was complete. The solvent was removed under reduced pressure. The crude material was redissolved in diethyl ether and washed with sat. aq. ammonium chloride and 1N HCl aqueous solution. The combined aqueous layer was reextracted with ethyl acetate three times. The combined organic layer was dried over MgSO4, filtered, and evaporated to a mixture of solid and oil. The crude was filtered to remove most of the oil, and the solid was washed with heptane. This yellow solid was triturated in a minimum amount of diethyl ether to wash off the yellow impurities. The material was filtered and the solid was retriturated with diethyl ether again. The filtrate was concentrated and the previous trituration steps were repeated. This afforded (I-36a) as a white solid (9.33 g, 61%); 1H NMR (400 MHz, CDCl3): δ 7.53 (1H), 7.30 (1H), 4.73 (2H), 3.81 (3H); m/z 209.0 (M+H)+.

1. stirringthe reaction was stirred for 3 h at room temperature
2. customThe solvent was removed under reduced pressure
3. dissolutionThe crude material was redissolved in diethyl ether
4. washwashed with sat. aq. ammonium chloride and 1N HCl aqueous solution
5. dry with materialThe combined organic layer was dried over MgSO4
6. filtrationfiltered
7. customevaporated to a mixture of solid and oil
8. filtrationThe crude was filtered
9. customto remove most of the oil
10. washthe solid was washed with heptane
11. customThis yellow solid was triturated in a minimum amount of diethyl ether
12. washto wash off the yellow impurities
13. filtrationThe material was filtered
14. customthe solid was retriturated with diethyl ether again
15. concentrationThe filtrate was concentrated

ORD record

ord-a876e03c48114d9c8c94969b9b988e91

Source dataset

uspto-grants-2011_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07977367B2