Sodium hydride → Tert-butyl 2-(4-(4-nitro-3-(trifluoromethyl)phenylamino)cyclohexyloxy)acetate

Participants

Reaction Conditions

Reaction Steps

In a 250 ml round-bottomed flask under nitrogen, a solution of 4-(4-nitro-3-trifluoromethyl-phenylamino)-cyclohexanol (10 g, 33 mmol) in 150 ml of THF was cooled using an external ice bath. Sodium hydride (3.65 g, 152 mmol, 3 eq) was then added and the mixture was stirred at ˜0° C. for 30 minutes before adding the tert-butyl-2-bromoacetate (9.6 g, 49.2 mmol, 1.5 eq). The solution was allowed to warm to room temperature while stirring overnight. The reaction was then diluted using 500 ml of ice-water. The mixture was then extracted with 3×200 ml of ethyl acetate. The organic layers were combined, dried over sodium sulfate, filtered, and concentrated under vacuum. The crude material was purified by silica gel chromatography using 10% ethyl acetate in petroleum ether to elute. The product-containing fractions were combined and concentrated under vacuum to provide 5 g (36%) of the desired ester as a yellow oil. Repeating this reaction on a larger scale yielded 51% of the desired product.

Provenance & Evidence