Dichloromethane → tert-Butyl 3(R)-[(1S,2S)-2-(Acetylamino)-3-(3,5-difluorophenyl)-1-hydroxypropyl]-5-(2,2-dimethylpropyl)-8-methoxy-3,4-dihydroisoquinoline-2(1H)-carboxylate

Participants

Reaction Steps

Dissolve tert-butyl 3(R)-[(1S,2S)-2-(acetylamino)-3-(3,5-difluorophenyl)-1-hydroxypropyl]-5-bromo-8-methoxy-3,4-dihydroisoquinoline-2(1H)-carboxylate (46.0 mg, 0.0808 mmol) in tetrahydrofuran (1.00 mL) in a sealed tube flushed with nitrogen. Add [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (1:1) (3.3 mg, 0.0040 mmol) and 0.500 M of neopentyl zinc iodide in tetrahydrofuran (0.808 mL) dropwise at room temperature. Stir the resulting green solution at room temperature for six hours. Heat to 50° C. for three days. Add saturated ammonium chloride solution (2 mL) and dilute with ethyl acetate (30 mL). Add water (10 mL) and separate the layers. Extract the aqueous layer (1×30 mL) with ethyl acetate. Combine the organic layers and dry over magnesium sulfate. Purify (Biotage medium pressure chormatography eluting with 1.5% methanol:dichloromethane) to give desired product (21.8 mg, 46%) as an off-white foam.

Provenance & Evidence