(+)-8-Phenylmenthol → (1R,2S,5R)-5-methyl-2-(1-methyl-1-phenylethyl)cyclohexyl 9-(3-bromo-4-fluorophenyl)-8-oxo-2,3,5,7,8,9-hexahydro-4H-pyrano[3,4-b]thieno[2,3-e]pyridine-4-carboxylate 1,1-dioxide

Participants

Reaction Steps

To a suspension of the product from Example 11D (1.58 g, 3.7 mmol) in THF (40 mL) at 0° C. under a nitrogen atmosphere was added a 1M solution of potassium tert-butoxide in THF (4.1 mL) dropwise over 5 minutes. The mixture was stirred at ambient temperature for 30 minutes, cooled to 0° C., treated with a solution of 8-phenylmenthol chloroformate prepared from (−)-8-phenylmenthol as described in (Yamamoto, Y., J. Amer. Chem. Soc. (1992), 114, 121-125) (1.31 g, 4.4 mmol) in THF (20 mL) over 5 minutes, stirred at ambient temperature for 16 hours, diluted with methylene chloride (150 mL) and washed with aqueous sodium bicarbonate (30 mL). The layers were separated and the aqueous layer was extracted with methylene chloride (50 mL). The combined organic layers were dried (MgSO4), filtered and concentrated. The residue was purified by flash chromatography over silica gel (3:2:1 chloroform/hexanes/diethyl ether) to provide 0.98 g of the less polar diasteriomer.

Provenance & Evidence