Potassium Phosphate, Tribasic → 1-(5-Ethylpyridin-2-yl)pyrrole-3-carboxylic acid

Temperature

100 °C

Tetrehydrofuran (7.2 ml) was added to 1-(5-chloropyridin-2-yl)pyrrole-3-carboxylic acid tert-butyl ester (1.0 g) described in Reference Example 55(1), palladium (II) acetate (80 mg), 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (S-Phos) (147 mg), vinylboronic acid pinacol ester (860 μl) and tripotassium phosphate (1.9 g) and stirred at 100° C. for 8.5 hours. Water was added to the reaction solution and extracted with ethyl acetate. The organic layer was washed with water and saturated brine, dried over anhydrous sodium sulfate and concentrated in vacuo. 1,4-Dioxane (15 ml) and 10% palladium-carbon (containing ca. 50% water; 200 mg) was added to the resulting residue and the mixture was stirred under hydrogen atmosphere at room temperature for six hours. The reaction solution was filtered through Celite and the filtrate was concentrated in vacuo. The residue was purified with silica gel column chromatography (n-hexane/ethyl acetate). To the resulting residue was added Dichloromethane (10 ml) and trifluoroacetic acid (3 ml) and the mixture was stirred at room temperature for 4.5 hours. Water was added to the reaction solution and the precipitated solid was washed with water. The resulting solid was dissolved in ethyl acetate, extracted with 4N aqueous solution of sodium hydroxide and the aqueous layer was acidified by the addition of 1N hydrochloric acid aqueous solution and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, concentrated in vacuo to give the titled compound (153 mg) as a white solid.

1. extractionextracted with ethyl acetate
2. washThe organic layer was washed with water and saturated brine
3. dry with materialdried over anhydrous sodium sulfate
4. concentrationconcentrated in vacuo
5. addition1,4-Dioxane (15 ml) and 10% palladium-carbon (containing ca. 50% water; 200 mg) was added to the resulting residue
6. stirringthe mixture was stirred under hydrogen atmosphere at room temperature for six hours
7. filtrationThe reaction solution was filtered through Celite
8. concentrationthe filtrate was concentrated in vacuo
9. customThe residue was purified with silica gel column chromatography (n-hexane/ethyl acetate)
10. additionTo the resulting residue was added Dichloromethane (10 ml) and trifluoroacetic acid (3 ml)
11. stirringthe mixture was stirred at room temperature for 4.5 hours
12. additionWater was added to the reaction solution
13. washthe precipitated solid was washed with water
14. dissolutionThe resulting solid was dissolved in ethyl acetate
15. extractionextracted with 4N aqueous solution of sodium hydroxide
16. additionthe aqueous layer was acidified by the addition of 1N hydrochloric acid aqueous solution
17. extractionextracted with ethyl acetate
18. dry with materialThe organic layer was dried over anhydrous sodium sulfate
19. concentrationconcentrated in vacuo

ORD record

ord-08fe1d53f9b04e339e6ae3b004df70af

Source dataset

uspto-grants-2015_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09150555B2