Diisopropylamine → Methyl (2z)-((3r,5r)-3-{[tert-butyl(diphenyl)silyl]oxy}-5-hydroxy-4-methylenecyclohexylidene)acetate

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Reaction Steps

A solution of diisopropylamine (1.2 mL, 9.4 mmol) in 10 mL of tetrahydrofuran was cooled to −78° C.; n-butyllithium (2.5 M in hexanes, 3.6 mL) was added, followed after 5 minutes by methyl trimethylsilylacetate (1.7 mL). The resultant solution was stirred at −78° C. for 30 minutes, and then a solution of the compound of Example 13E (2.0 g, 4 mmol) in 10 mL of tetrahydrofuran was added over 5 minutes. Stirring was continued for 4 hours. The reaction was quenched by addition of saturated aqueous NH4Cl; the mixture was warmed to ambient temperature, and partitioned between ethyl acetate and water. The organic phase was washed with 1 N aqueous HCl and brine, and dried over Na2SO4. The solvents were removed in vacuo; the residue was purified by chromatography on an Analogix Intelliflash 280™, eluting with a gradient of 5% to 10% ethyl acetate in hexanes. The product (1.9 g) was dissolved in 17 mL of ethanol; 1.3 mL of concentrated HCl was added, and the resultant solution was stirred overnight at ambient temperature. The solvents were removed in vacuo, the residue was taken up in saturated aqueous sodium bicarbonate solution and extracted with ethyl acetate. The organic phase was concentrated in vacuo and purified by chromatography on an Analogix Intelliflash 280™, eluting with a gradient of 2% to 3% dichloromethane in acetonitrile to afford the titled compound (0.76 g).

Provenance & Evidence