Iodine → HCID 68183132, 화합물

온도

-78 °C

To a stirring solution of 4-(3,4-dichlorophenyl)-4,5,6,7-tetrahydro-8H-thieno[2,3-c]azepin-8-one (1.05 g, 3.36 mmol) in tetrahydrofuran (30 mL) at −78° C. was added a solution of n-butyllithium in hexane (2.5 M, 6.73 mL, 16.82 mmol) in rapid drops under an atmosphere of argon. The reaction solution became purplish after ˜2 ml had been added and became intensely purple by the end of the addition. The reaction solution was stirred at −78° C. for 30 minutes then iodine (7.95 g, 31.3 mmol) was added as a solid in a single portion with good stirring—the purple color was instantly quenched to give a reddish brown mixture. The resulting mixture was stirred at −78° C. for 5 minutes then the dry ice/acetone bath was removed and the reaction was allowed to warm to rt with stirring for one hour. A saturated sodium bisulfate solution (150 mL) was added to the reaction mixture with good stirring—most of the color faded to give a lemon yellow mixture. Ethyl acetate was added and the mixture was transferred to a separatory funnel. The organic layer was separated, the aqueous layer was extracted with ethyl acetate, the combined organic layers were washed with saline, dried over sodium sulfate, filtered, and concentrated to leave crude product as a light orange solid. The crude product was stirred with DCM—most solids did not dissolve. The mixture was sonicated well, diluted with t-butyl methyl ether, and the white precipitate was isolated on a fritted funnel. It was washed it with additional TBME and air-dried to leave 787 mg product as a white powder. The filtrate was evaporated to leave an orange residue which was purified using column chromatography on silica gel (80 g RediSep column, gradient 0% ethyl acetate in hexane to 100% ethyl acetate in hexane over 30 minutes) to give 440 mg additional product as a white solid. Total yield 1.227 g (83% yield). LCMS: (FA) ES+ 438, 440. 1H NMR (400 MHz, DMSO) δ 8.27-8.20 (d, J=4.5 Hz, 1H), 7.61-7.53 (d, J=8.3 Hz, 1H), 7.47-7.42 (d, J=2.0 Hz, 1H), 7.09-7.02 (dd, J=8.3, 2.1 Hz, 1H), 6.81-6.75 (s, 1H), 4.51-4.41 (dd, J=8.6, 5.3 Hz, 1H), 3.22-3.05 (d, J=5.5 Hz, 2H), 2.27-2.14 (m, 1H), 2.09-1.99 (m, J=7.9 Hz, 1H).

1. additionhad been added
2. additionbecame intensely purple by the end of the addition
3. customwas instantly quenched
4. customto give a reddish brown mixture
5. stirringThe resulting mixture was stirred at −78° C. for 5 minutes
6. customthe dry ice/acetone bath was removed
7. temperatureto warm to rt
8. stirringwith stirring for one hour
9. additionA saturated sodium bisulfate solution (150 mL) was added to the reaction mixture
10. stirringwith good stirring—most of the color
11. customto give a lemon yellow mixture
12. customthe mixture was transferred to a separatory funnel
13. customThe organic layer was separated
14. extractionthe aqueous layer was extracted with ethyl acetate
15. washthe combined organic layers were washed with saline
16. dry with materialdried over sodium sulfate
17. filtrationfiltered
18. concentrationconcentrated
19. customto leave crude product as a light orange solid
20. dissolutiondid not dissolve
21. customThe mixture was sonicated well
22. customthe white precipitate was isolated on a fritted funnel
23. washIt was washed it with additional TBME
24. customair-dried

ORD 기록

ord-e4adf09c9e3f41d7935035168b23966d

출처 데이터셋

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08765746B2