Water → (5s)-5-(Acetylamino)-9,10,11-trimethoxy-6,7-dihydro-5h-dibenzo[a,c]cyclohepten-3-yl hydrogen methylphosphonate

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Reaction Conditions

Reaction Steps

A solution of N-acetyl-colchicinol (0.36 g; 1.0 mmol) in THF (40 ml) under argon was cooled to 0° C. and treated with a 1.0M solution of lithiumHMDS in THF (1.1 ml; 1.1 mmol). The mixture was stirred at 0° C. for 1 hour and then added in portions over about 2 hours to a solution of methylphosphonic dichloride (0.53 mg; 4.0 mmol) in THF (150 ml). The mixture was stirred at ambient temperature for 15 minutes. After addition of water (200 ml) the THF was removed by evaporation. After removal of the insoluble material by filtration, the filtrate was purified on HP20 SS resin eluting with a gradient of 0–60% methanol/water. The methanol was removed by evaporation and the mixture was adjusted to pH7.14 with sodium hydroxide (0.1 M). The appropriate fractions were freeze-dried to give (5S)-5-(acetylamino)-9,10,11-trimethoxy-6,7-dihydro-5H-dibenzo[a,c]cyclohepten-3-yl hydrogen methylphosphonate as a beige solid (180 mg).

Provenance & Evidence