Chlorotrimethylsilane → (R)-4-dimethylamino-1-(2-methyl-5-(triethylsilyl)pent-4-inyl)-4-phenylcyclohexanol

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Reaction Steps

A 1.7 M solution of tert-butyl lithium (7.8 mL, 13.3 mmol) in pentane was added in drops to a solution of triethyl-((R)-5-iodo-4-methylpent-1-inyl)silane (2.15 g, 6.6 mmol) in anhydrous diethyl ether (100 mL) at −85° C. in argon, wherein the inside temperature was held at −85° C. After stirring for 2 h at −85° C. a solution of 4-dimethylamino-4-phenylhexanone (1.43 g, 6.6 mmol) in anhydrous diethyl ether (30 mL) was added in drops at this temperature and stirred for a further 30 min. A solution of trimethylchlorosilane (1.44 g, 1.69 mL, 13.3 mmol) in diethyl ether (12 mL) was then added to the solution in drops and slowly heated to room temperature. The reaction mixture was then mixed with saturated ammonium chloride solution (20 mL) and the separated solid (2.00 g) was filtered off. The phases were separated and the aqueous [phase?] extracted with diethyl ether (3×30 mL). The combined diethyl ether phases were washed with sodium chloride solution (20 mL), dried with sodium sulphate, filtered and concentrated to low volume in a vacuum. No target product could be isolated from this phase. The separated solid (2.00 g) was then mixed with saturated sodium hydrogencarbonate solution (50 mL) and the resulting suspension extracted with ethyl acetate (3×30 mL). The combined ethyl acetate phases were dried with sodium sulphate and concentrate to low volume in a vacuum. The raw product (351 mg) was purified by flash chromatography (18 g, 20×2.0 cm) with ethyl acetate/cyclohexane (1:2).

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