Baccatin Iii → Taxane

Participants

Reaction Steps

Coupling reaction: the C-7 triethylsilylprotected baccatin III (0.048 g; 0.0685 mmol) and the triethylsily-isopropyl-β-lactam (3) (0.043 g; 0.0978 mmol; 1.4 eq.) were dissolved in 3.6 ml dry tetrahydrofuran. The solution was cooled to a temperature in the range −45° C. to −50° C. (dry ice-acetonitrile bath) under nitrogen. The base sodium bistrimethylsilylamide (NaHMDS) (1.0 M) solution in tetrahydrofuran; 0.175 ml; 175 mmol; 2.6 eq) was added in one portion at a temperature of −45° C. and the reaction was stirred for 30 min at this temperature. The solution became yellow and was quenched at 30 min with an ammonium chloride saturated solution. The work up consisted of quenching the reaction with saturated ammonium chloride, extracting with ethyl acetate, washing the organic phase with brine and drying the organic layer with magnesium sulphate. After filtration the solvent was evaporated and flash chromatography of the residue with 20% ethyl acetate/hexane in a 6″ chromatography column; 36 mg of the coupled protected taxane (5) was obtained with 14 mg of starting material recovered (4, uncoupled protected baccatin III).

Provenance & Evidence