Citric Acid → HCID 117700629, compound

Temperature

90 °C

A suspension of the [4-methoxy-3-(3,3,6,6-tetramethyl-1,8-dioxo-2,3,4,5,6,7,8,9-octahydro-1H-xanthen-9-yl)phenyl]boronic acid produced in Example 1-1 (2.41 g, 5.68 mmol), 6-bromopyridine-2-carboxylic acid (1.17 g, 5.68 mmol), sodium carbonate (2.41 g, 22.7 mmol), and tetrakis(triphenylphosphine) palladium(0) (0.33 g, 0.28 mmol) in 1,2-dimethoxyethane (48.2 ml) and water (21 ml) was prepared at room temperature, and the prepared suspension was then stirred at 90° C. for 4 hours. After air-cooling, a 10% aqueous solution of citric acid was added to the reaction solution, and the mixed solution was then extracted with dichloromethane three times. The organic layer thus obtained was dried over anhydrous sodium sulfate. The solvent was distilled away under reduced pressure, and the residue thus obtained was then dissolved in THF (48 ml). Thereafter, an aqueous solution of lithium hydroxide monohydrate (524 mg, 12.5 mmol) was added to the solution obtained above, and the mixture thus obtained was then stirred at room temperature. Water was added to the reaction solution, and the resulting solution was then washed with diethyl ether. Thereafter, a 1 N aqueous solution of hydrochloric acid (12.5 ml) was added to the water layer, and the resultant was then extracted with dichloromethane four times. The organic layer thus obtained was dried over anhydrous sodium sulfate. The solvent was distilled away under reduced pressure, and the residue thus obtained was then purified by silica gel column chromatography (methanol:dichloromethane=3:97 to 4:96, v/v). The solid thus obtained was washed with a mixed solution of diethyl ether and hexane, followed by collection by filtration and drying, to obtain the title compound (2.19 g, yield: 77%).

1. customwas prepared at room temperature
2. temperatureAfter air-cooling
3. extractionthe mixed solution was then extracted with dichloromethane three times
4. customThe organic layer thus obtained
5. dry with materialwas dried over anhydrous sodium sulfate
6. distillationThe solvent was distilled away under reduced pressure
7. customthe residue thus obtained
8. customobtained above, and the mixture
9. customthus obtained
10. stirringwas then stirred at room temperature
11. washthe resulting solution was then washed with diethyl ether
12. additionThereafter, a 1 N aqueous solution of hydrochloric acid (12.5 ml) was added to the water layer
13. extractionthe resultant was then extracted with dichloromethane four times
14. customThe organic layer thus obtained
15. dry with materialwas dried over anhydrous sodium sulfate
16. distillationThe solvent was distilled away under reduced pressure
17. customthe residue thus obtained
18. customwas then purified by silica gel column chromatography (methanol
19. customThe solid thus obtained
20. washwas washed with a mixed solution of diethyl ether and hexane
21. filtrationfollowed by collection by filtration
22. customdrying

ORD record

ord-6b692e4b5c5e47c1af08fbc8de5709e1

Source dataset

uspto-grants-2015_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08975263B2