Methyl 2-(3,5-bis(trifluoromethyl)phenyl)-2-diazoacetate → (1R*,2R*,5S*,6R*)-8-Benzyl-2-{(1R*)-1-[3,5-bis(trifluoromethyl)phenyl]-(methoxycarbonyl)methoxy}-6-cyano-1-phenyl-8-azabicyclo[3.2.1]octane

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Reaction Steps

A mixture of (1R*,2R*,5S*,6R*)-8-benzyl-6-cyano-1-phenyl-8-azabicyclo[3.2.1]octan-2-ol (Description 31; 7.186 g, 22.6 mmol) and rhodium(II) acetate dimer (0.216 g, 0.452 mmol) in benzene (30 ml) was heated to reflux, and treated slowly with a solution of methyl 2diazo-2-(3,5-bis(trifluoromethyl)phenyl)-acetate [prepared by the method of R. T. Lewis et al. J. Org. Chem., 2000, 65, 2615] (7.7563 g, 24.86 mmol) in benzene (30 ml). After the addition was complete the mixture was concentrated in vacuo and the residue purified by flash column chromatography, eluting with 10-20% ethyl acetate/hexane to give a mixture of diastereomers (6.0 g, 2.6:1 ratio). The major diastereomer was separated by crystallisation with ethyl acetate/hexane to afford the title compound in two crops (3.81 g).

Provenance & Evidence