Methanesulfonic Acid → HCID 18407230, compound

Temperature

-60 °C

13.26 g of 3-bromopyridine are dissolved in 160 ml of diethyl ether and cooled to −60° C. To this solution are added dropwise over the course of 30 minutes 52 ml of a 1.6 molar solution of n-butyllithium in n-hexane. The solution is allowed to warm to −30° C. and, at this temperature, 9.5 ml of trimethyl borate are added dropwise with stirring. The reaction mixture is subsequently heated under reflux for 3 hours and then cooled to 0° C., and 6.1 ml of 1,3-propanediol are added dropwise. This mixture is stirred at 0° C. for 30 minutes before adding 5.46 ml of methanesulfonic acid dropwise and stirring for a further 30 minutes. Then 20 g of Celite are added, the mixture is warmed to room temperature and filtered, the filtrate is concentrated, the residue is stirred in 700 ml of toluene and, after renewed filtration, the solvent is removed by distillation in vacuo. 4.1 g of the residue (3[1,3,2]dioxaborinan-2-ylpyridine) are dissolved, without further purification, together with 4.22 g of 5-bromo-1-indanone and 4.24 g of sodium carbonate in a mixture of 100 ml of toluene with 20 ml of ethanol and 20 ml of water. The solution is degassed with argon and then 112 mg of palladium(II) acetate and 262 mg of triphenylphosphine are added. The reaction mixture is boiled under reflux for 4 hours and cooled to room temperature, and the ethanol content in the mixture is removed by distillation in vacuo. Then 50 ml of a 0.5 N sodium hydroxide solution are added with stirring, the organic phase is separated off and the aqueous phase is extracted by shaking with toluene. The combined organic phases are extracted by shaking successively with water and saturated brine, dried over magnesium sulfate, concentrated in vacuo and purified by chromatography on silica gel with 1/1 ethyl acetate/n-heptane. 5-Pyridin-3-yl-1-indanone is obtained with a melting point of 103-106° C.

1. additionare added dropwise
2. temperatureThe reaction mixture is subsequently heated
3. temperatureunder reflux for 3 hours
4. temperaturecooled to 0° C.
5. stirringThis mixture is stirred at 0° C. for 30 minutes
6. stirringstirring for a further 30 minutes
7. additionThen 20 g of Celite are added
8. temperaturethe mixture is warmed to room temperature
9. filtrationfiltered
10. concentrationthe filtrate is concentrated
11. stirringthe residue is stirred in 700 ml of toluene
12. filtrationfiltration
13. customthe solvent is removed by distillation in vacuo
14. dissolution4.1 g of the residue (3[1,3,2]dioxaborinan-2-ylpyridine) are dissolved, without further purification, together with 4.22 g of 5-bromo-1-indanone and 4.24 g of sodium carbonate in a mixture of 100 ml of toluene with 20 ml of ethanol and 20 ml of water
15. customThe solution is degassed with argon
16. addition112 mg of palladium(II) acetate and 262 mg of triphenylphosphine are added
17. temperatureunder reflux for 4 hours
18. temperaturecooled to room temperature
19. customthe ethanol content in the mixture is removed by distillation in vacuo
20. additionThen 50 ml of a 0.5 N sodium hydroxide solution are added
21. stirringwith stirring
22. customthe organic phase is separated off
23. extractionthe aqueous phase is extracted
24. stirringby shaking with toluene
25. extractionThe combined organic phases are extracted
26. stirringby shaking successively with water and saturated brine
27. dry with materialdried over magnesium sulfate
28. concentrationconcentrated in vacuo
29. custompurified by chromatography on silica gel with 1/1 ethyl acetate/n-heptane

ORD record

ord-838a5a9d3daf438fba4c2066aa68de4e

Source dataset

uspto-grants-2002_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06476059B1