2-Methyl-2-butanol → t-Amyl 2,5,6-trichloronicotinate

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Reaction Steps

The product of Example 11 (2.5 g, 11 mmol) was slurried in thionyl chloride (30 mL) containing 2 drops of dry dimethylformamide (DMF). The slurry was heated to reflux at which time all components fully dissolved into solution. Reflux was continued for an additional three hours. After cooling to ambient temperature, the excess thionyl chloride was removed in vacuo and the resulting oily residue was taken up in diethyl ether (Et2O) (20 mL) and cooled to 0° C. in an ice bath. A solution of t-amyl alcohol (0.88 g, 10 mmol) in Et2O (15 mL) was cooled to -10° C. in a dry ice bath and n-butyllithium (1.6 M solution in hexanes, 6.5 mL, 1 eq) was added dropwise over 10 minutes, keeping the temperature below 0° C. The solution was warmed to ambient temperature, charged to an addition funnel under nitrogen and added dropwise to the nitrogen-purged ethereal solution of the acyl chloride prepared above. After complete addition, the solution was warmed to ambient temperature with stirring overnight. The solution was washed with saturated brine (3×200 mL) and the organics were dried over Na2SO4, filtered, and the solvent removed in vacuo to give t-amyl 2,5,6-trichloronicotinate (92.46 g) as an orange oil.

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