反应详情

温度

120 °C

(1S,2R,4S)-ethyl 4-(4-((2-(3,5-dichloro-2-methoxypyridin-4-yl)ethyl)(neopentyl)carbamoyl)-5-(trifluoromethyl)-1H-pyrazol-1-yl)-2-methylcyclohexanecarboxylate (109 mg, 0.175 mmol) was treated with aqueous hydrochloric acid (5.0 N, 3.00 mL, 15.00 mmol) and hydrochloric acid (4.0 N in 1,4-dioxane, 3.00 mL, 12.00 mmol), fitted with a reflux condenser and heated to 120° C. for 3 h. The reaction mixture was concentrated to dryness under reduced pressure (rotary evaporator) and the crude residue was purified on a Gilson (Gemini™ Phenomenex; 30×150 mm, 5 u, using a gradient of 10-95% 0.1% TFA/CH3CN in 0.1% TFA/water), concentrated in a genevac overnight affording (1S,2R,4S)-4-(4-((2-(3,5-dichloro-2-oxo-1,2-dihydropyridin-4-yl)ethyl)(neopentyl)carbamoyl)-5-(trifluoromethyl)-1H-pyrazol-1-yl)-2-methylcyclohexanecarboxylic acid (57 mg, 0.098 mmol, 56% yield) as a white amorphous solid. MS (ESI) 579.0, 581.2 [M+H]+.

1. customfitted with a reflux condenser
2. concentrationThe reaction mixture was concentrated to dryness under reduced pressure (rotary evaporator)
3. customthe crude residue was purified on a Gilson (Gemini™ Phenomenex
4. concentrationconcentrated in a genevac overnight