Trimethyl Phosphate → HCID 10975655, compound

Participants

Reaction Steps

To 37.78 g (0.286 mol) of 6-hydroxyindoline 5 in a 100 ml round-bottom flask fitted with a magnetic stirrer, thermometer and condenser connected to a source of nitrogen was added 13.38 ml (16.02 g, 0.114 mol) of trimethyl phosphate. It was then placed in an oil bath and heating was commenced. The bath temperature reached 105° in 10 min. Then the reaction mixture became homogeneous and shortly thereafter an exotherm occurred. The flask was removed periodically from the oil bath to keep the internal temperature below 150°. The reaction was heated at 140°-150° for 2 hr. Thin layer chromatography on silica gel plates eluted with 50% Ethyl acetate/hexane or 4% methanol/methylene chloride showed that starting material was still present and 3 ml (3.59 g, 25.6 mmol) more of trimethyl phosphate was added. Heating was continued at 155° for 1.5 hr. The reaction mixture was allowed to cool and then dissolved in 100 ml of saturated sodium carbonate solution and 100 ml of methylene chloride with warming in portions. The aqueous phase was separated and washed with 2×100 ml of methylene chloride. The organic phases were combined, washed with 200 ml of half-saturated brine, dried over sodium sulfate and concentrated in vacuo to leave 28.6 g (67%) of dark tar. This was dissolved in methylene chloride and filtered through 300 ml of silica gel in methylene chloride. A total of 800 ml of methylene chloride eluate and then 400 ml of ethyl acetate was collected. Concentration and collection of the residue from hexane gave 18.29 g (43%) of crude product 7 as a brown solid which was used for the preparation of 9.

Provenance & Evidence