Citric Acid → 1516805-43-8

A lanthanum(III) chloride-bis(lithium chloride) complex (0.6 M solution in THF, 16.7 mL, 10 mmol) was added to a solution of 1-(6-bromopyridin-3-yl)ethanone (2 g, 10 mmol) in THF (10 mL), and the mixture was stirred at room temperature for 1 hour. Methyl magnesium bromide (1.12 M solution in THF, 10.7 mL, 12 mmol) was added thereto at 0° C., and the mixture was stirred for 1 hour. A 10% citric acid aqueous solution was added to the reaction solution, and the solvent was distilled off under reduced pressure. The residue was diluted with ethyl acetate, and insoluble matter was filtered off through Celite. After extraction with ethyl acetate twice, combined organic layers were washed with brine and dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. An internal salt of (methoxycarbonylsulfamoyl)triethylammonium hydroxide (2.86 g, 12 mmol) was added to a solution of the obtained residue in THF (20 mL), and the mixture was stirred at 60° C. for 2 hours. The solvent in the reaction solution was distilled off under reduced pressure, and ethyl acetate was added to the residue. The organic layer was washed with brine and dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography [elute: hexane/ethyl acetate=98/2-80/20 (gradient)] to obtain the title compound (1.00 g, yield: 51%).

1. stirringat 0° C., and the mixture was stirred for 1 hour
2. distillationthe solvent was distilled off under reduced pressure
3. additionThe residue was diluted with ethyl acetate, and insoluble matter
4. filtrationwas filtered off through Celite
5. extractionAfter extraction with ethyl acetate twice
6. washwere washed with brine
7. dry with materialdried over anhydrous sodium sulfate
8. distillationthe solvent was distilled off under reduced pressure
9. stirringthe mixture was stirred at 60° C. for 2 hours
10. distillationThe solvent in the reaction solution was distilled off under reduced pressure, and ethyl acetate
11. additionwas added to the residue
12. washThe organic layer was washed with brine
13. dry with materialdried over anhydrous sodium sulfate
14. distillationthe solvent was distilled off under reduced pressure
15. customThe obtained residue was purified by silica gel column chromatography [elute: hexane/ethyl acetate=98/2-80/20 (gradient)]

ORD record

ord-ea77735260264faca641b5e59e6de05f

Source dataset

uspto-grants-2015_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09150575B2