Benzene → Ethyl 4-(2-(2,2,2-trifluoroacetyl)-1,2,3,4-tetrahydroisoquinolin-5-yl)butanoate

Participants

Reaction Steps

A mixture of 1-(5-bromo-3,4-dihydroisoquinolin-2(1H)-yl)-2,2,2-trifluoroethanone (4.0 g, 13 mmol) and Pd(dppf)Cl2.CH2Cl2 (530 mg, 0.65 mmol) was azeotroped with benzene and suspended in 50 mL of dry THF. At room temperature, 4-ethoxy-4-oxobutylzinc bromide (0.5M in THF, 52 mL, 26 mmol) was added dropwise with syringe. The orange suspension became a clear brown solution. The reaction mixture was then refluxed for 1 h. After cooling to room temperature, it was quenched with brine, extracted with EtOAc, washed with 10% HCl and brine, dried over Na2SO4, and evaporated to dryness. Flash chomatography (SiO2, EtOAc/hexane=15:100 to 20:100) gave ethyl 4-(2-(2,2,2-trifluoroacetyl)-1,2,3,4-tetrahydroisoquinolin-5-yl)butanoate as a white solid.

Provenance & Evidence