Trimethyl Phosphate → HCID 10975655, compound

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.

1. customthermometer and condenser connected to a source of nitrogen
2. customIt was then placed in an oil bath
3. temperatureheating
4. customThe flask was removed periodically from the oil bath
5. customthe internal temperature below 150°
6. temperatureThe reaction was heated at 140°-150° for 2 hr
7. washThin layer chromatography on silica gel plates eluted with 50% Ethyl acetate/hexane or 4% methanol/methylene chloride
8. addition3 ml (3.59 g, 25.6 mmol) more of trimethyl phosphate was added
9. temperatureHeating
10. waitwas continued at 155° for 1.5 hr
11. temperatureto cool
12. dissolutiondissolved in 100 ml of saturated sodium carbonate solution
13. temperature100 ml of methylene chloride with warming in portions
14. customThe aqueous phase was separated
15. washwashed with 2×100 ml of methylene chloride
16. washwashed with 200 ml of half-saturated brine
17. dry with materialdried over sodium sulfate
18. concentrationconcentrated in vacuo
19. customto leave 28.6 g (67%) of dark tar
20. filtrationfiltered through 300 ml of silica gel in methylene chloride
21. customA total of 800 ml of methylene chloride eluate and then 400 ml of ethyl acetate was collected
22. concentrationConcentration and collection of the residue from hexane

ORD record

ord-f0f090d3999a4140baf01b8f58b9f89d

Source dataset

uspto-grants-1993_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05256799