Pyridine → HCID 11206952, compound

1.9 g (0.01 mole) of CuI was added to a mixture of 18.7 g (0.236 mole) of pyridine and 300 ml of tetrahydrofuran under a N2 atmosphere with stirring. The mixture was stirred at room temperature until the mixture became a homogeneous solution, and thereafter a solution of 22.8 g (0.21 mole) of ethyl chloroformate and 20 ml of tetrahydrofuran was added dropwise, on an ice bath, so that the inner temperature of the reactor could not exceed 20° C. Further, 100 ml of 2M phenyl magnesium chloride solution (0.2 mole; THF solution) was added dropwise over 1.5 hours at the inner temperature ranging from −10° C. to −5° C. The reaction mixture was stirred for 0.5 hours at the temperature of −10° C. to −5° C. Further, after stirring for 1 hour at 25° C., about 150 ml of tetrahydrofuran was removed from the mixture by a vacuum distillation, and then 180 ml of aqueous 20% ammonium chloride solution was added to the resultant mixture. The reaction product was extracted with 180 ml of ethyl acetate, and then the aqueous layer was discharged. Thereafter, 180 ml of 10% hydrochloric acid was added and stirred for 15 minutes. The resulting precipitate was removed by filtration through celite, and then the celite was washed with 40 ml of ethyl acetate. After removing the aqueous layer of the filtrate, the organic layer was washed once with 180 ml of 10% hydrochloric acid, and twice with 180 ml each of water. The organic layer was concentrated under a reduced pressure to obtain Compound I-1: obtained amount 44.6 g; purity 88.0% (determined by HPLC); yield 85.5%.

1. stirringThe mixture was stirred at room temperature until the mixture
2. customexceed 20° C
3. customranging from −10° C. to −5° C
4. stirringThe reaction mixture was stirred for 0.5 hours at the temperature of −10° C. to −5° C
5. stirringFurther, after stirring for 1 hour at 25° C.
6. customabout 150 ml of tetrahydrofuran was removed from the mixture by a vacuum distillation
7. addition180 ml of aqueous 20% ammonium chloride solution was added to the resultant mixture
8. extractionThe reaction product was extracted with 180 ml of ethyl acetate
9. additionThereafter, 180 ml of 10% hydrochloric acid was added
10. stirringstirred for 15 minutes
11. customThe resulting precipitate was removed by filtration through celite
12. washthe celite was washed with 40 ml of ethyl acetate
13. customAfter removing the aqueous layer of the filtrate
14. washthe organic layer was washed once with 180 ml of 10% hydrochloric acid
15. concentrationThe organic layer was concentrated under a reduced pressure
16. customto obtain Compound I-1
17. customobtained amount 44.6 g

ORD record

ord-7e8e69a6810948b2833532a6f4098788

Source dataset

uspto-grants-2004_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06762303B2