Formaldehyde → 2-Trifluoroacetyl-7-trifluoromethyl-1,2,3,4-tetrahydroisoquinoline

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Reaction Steps

2,2,2-Trifluoro-N-{2-[4-(trifluoromethyl)phenyl]ethyl}acetamide (4.00 g, 14 mmol) and paraformaldehyde (0.63 g) were combined in a flask and dissolved in acetic acid (11 mL). Sulfuric acid (11 mL) was added slowly. The mixture went from a cloudy solution to clear and an exothermic reaction was observed. After 40 min, the flask was lowered into an ice bath. The reaction was quenched with cold water and the resulting solution was extracted with EtOAc three times. The combined extracts were washed with water, saturated sodium bicarbonate and brine, dried (MgSO4), filtered, and concentrated to afford a yellow oil (4.1 g, 83%). MS calculated for C12H9F6NO: (M+H)+298; found 298.0.

Provenance & Evidence