Triphenylphosphine → 1-tert-Butyl 2-methyl (2S,4R)-4-[(2-ethoxy-6-vinylquinazolin-4-yl)oxy]pyrrolidine-1,2-dicarboxylate

Participants

Reaction Conditions

Reaction Steps

A solution of 2-ethoxy-6-iodoquinazolin-4-ol (2.94 g, 9.30 mmol) and 1-tent-butyl 2-methyl (2S,4S)-4-hydroxypyrrolidine-1,2-dicarboxylate (2.28 g, 9.30 mmol) in THF (150 ml) was cooled to 0° C. and treated with Ph3P (2.93 g, 11.16 mmol). DEAD (4.42 ml, 11.16 mmol) was added dropwise, and the mixture was stirred at 20° C. for 4 h. After evaporation of the volatiles, the residue was purified on silica gel (gradient elution, 0-5% EtOAc/(EtOAc:DCM=5:95)) to furnish a 6:4 mixture of 1-tert-butyl 2-methyl (2S,4R)-4-[(2-ethoxy-6-iodoquinazolin-4-yl)oxy]pyrrolidine-1,2-dicarboxylate and 1-text-butyl 2-methyl (2S,4R)-4-(2-ethoxy-6-iodo-4-oxoquinazolin-3(4H)-yl)pyrrolidine-1,2-dicarboxylate (3.8 g) LCMS (ES+) m/z 544 (M+H)+. This material was dissolved in EtOH (40 mL) and treated with TEA (0.83 mL, 5.98 mmol). Potassium vinyltrifluoroborate (0.80 g, 5.98 mmol) and PdCl2(dppf)-CH2Cl2 adduct (0.32 g, 0.399 mmol) were added, and the mixture was stirred at 90° C. for 2 h. The mixture cooled, diluted with EtOAc and washed with aqueous HCl (1 N) and brine. The organic phase was dried over Na2SO4, filtered and concentrated to give a residue that was purified on silica (gradient elution, 0-20% EtOAc/DCM) to yield the title compound as an oil (1.38 g, 33%). LCMS (ES+) m/z 444 (M+H)+.

Provenance & Evidence