Phenyl triflimide → (+/-)-tert-Butyl-2-({[tert-butyl(diphenyl)silyl]oxy}methyl)-3-(2,5-difluorophenyl)-5-phenyl-2,5-dihydro-1H-pyrrole-1-carboxylate

Participants

Reaction Steps

A solution of the carbinol 1-6 (36 g, 67.7 mmol) in CH2Cl2 (400 mL) was treated with Dess-Martin periodinane (29 g, 67.7 mmol). After stirring for 1 h at rt the reaction was quenched with a 1:1 (200 mL) solution of Na2S2O3/NaHCO3 and the mixture stirred vigorously for 2 h. The reaction was extracted with CH2Cl2 (2×200 mL) and the combined organic solutions dried over MgSO4, filtered, and concentrated. The residue (35.5 g, 67.0 mmol) was dissolved in THF (500 mL) and cooled to −78° C. The solution was treated with NaHMDS (83.0 mL of a 1M soln in THF, 83 mmol) and stirred at −78° C. for 1 h. Neat Tf2NPh (28.7 g, 80.4 mmol) was added to the reaction and the reaction was stirred with gradual warming to rt for 12 h. The reaction was diluted with EtOAc and washed with satd aq NH4Cl and brine. The organic solution was dried over MgSO4, filtered and concentrated. The residue (44.3 g, 66.9 mmol) was dissolved in dioxane (300 mL) and 2M Na2CO3 (100 mL). The mixture was degassed with a flow of N2 (g) for 30 min and treated with 2,5-difluorophenylboronic acid (13.7 g, 87 mmol) and tetrakis(triphenylphosphine)-palladium (3.8 g, 3.3 mmol). The yellow mixture was heated at 90° C. for 90 min, cooled to rt, and diluted with EtOAc (300 mL). The organic solution was washed with satd aq NH4Cl (150 mL), dried over MgSO4, filtered, and concentrated. The residue was purified by flash chromatography (SiO2; 20/80 CH2Cl2/hexanes to 10% EtOAc/hexanes) to provide the desired product diastereomers 1-7 as a yellow foam. LRMS (m/z) M+1 expected 627, found 627.

Provenance & Evidence