Chloromethyl Methyl Ether → 9a-butyl-7-methoxymethoxy-4-methyl-1,2,9,9a-tetrahydro-3H-fluoren-3-one

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Reaction Steps

A solution of 9a-butyl-7-hydroxy-4-methyl-1,2,9,9a-tetrahydro-3H-fluoren-3-one (5.30 g, 21 mmol) in anhydrous dimethylformamide (50 mL) was cooled in an ice bath, stirred under a nitrogen atmosphere, and treated successively with N,N-diisopropyl-ethylamine (10.5 mL, 60 mmol) and chloromethyl methyl ether (3.45 mL, 41 mmol). The resulting mixture was stirred while gradually warming to room temperature over 5 hours. After 5.5 hours, additional N,N-diisopropyl-ethylamine (3 mL) and chloromethyl methyl ether (1 mL) were added. After stirring an additional 25 minutes at room temperature, the reaction mixture was diluted with EtOAc (1 L) and washed with 1.3N HCl (1 L). The aqueous phase was separated and extracted with EtOAc (200 mL). The combined organics were washed with 5% NaHCO3 (500 ml) and brine, dried over MgSO4, filtered, and concentrated under vacuum to an orange oil (6.5 g). This material was divided into three portions and each purified by flash chromatography on silica gel using Biotage FLASH 40M columns and 10:1 hexanes-EtOAc as eluting solvent. The product containing fractions were combined and evaporated under vacuum to afford 9a-butyl-7-methoxymethoxy-4-methyl-1,2,9,9a-tetrahydro-3H-fluoren-3-one (4.98 g) as an oil.

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