1,3-Dichloro-5,5-dimethylhydantoin → HCID 117737133, compound

Temperature

0 °C

A flask was charged with 6-(benzylthio)-1-(5-chloro-2-methoxy-4-(trifluoromethyl)phenyl)quinolin-2(1H)-one (1.63 g, 3.43 mmol), MeCN (16.11 ml), AcOH (0.612 ml), and water (0.403 ml). The heterogeneous mixture was cooled to 0° C. for 10 min. 1,3-dichloro-5,5-dimethylimidazolidine-2,4-dione (0.675 g, 3.43 mmol) was added portionwise (5 portions 0.135 g each, each portion added over 5 min., 20-30 min apart). After 3.5 h the reaction was not complete by LCMS, so another 0.25 equiv (0.1688 g) of hydantoin was added, followed by another 0.25 equiv. hydantoin at 4 h. With the reaction still at 0° C., 2,3,4,5,6-pentafluorophenol (0.757 g, 4.11 mmol) was added to the reaction flask, along with MeCN (2 mL). After 10 minutes, triethylamine (1.910 ml, 13.70 mmol) was added dropwise over 1 min. The reaction was allowed to stir at 0° C. After for 30 min, 1:1 brine:water (20 mL) was added, then EtOAc (20 mL). The layers were separated and the aqueous layer was extracted again with 20 mL EtOAc. The combined organics were dried with sodium sulfate, filtered and concentrated to give a brown sticky solid, which was taken up in 75 mL iPrOH (with 10 min sonication), then let stand for 20 min. A white powdery solid crashed out and was collected by filtration through a medium glass frit, the solid washed with iPrOH and dried under high vac. The filtrate was also concentrated to dryness and purified by Biotage, 100 g SNAP Ultra silica col, loaded in minimal DCM onto dry column and purified with a gradient from 2-50% EtOAc/heptane. Fractions with product were combined with the filtered crystals and concentrated under high vac to provide perfluorophenyl 1-(5-chloro-2-methoxy-4-(trifluoromethyl)phenyl)-2-oxo-1,2-dihydroquinoline-6-sulfonate (1.7957 g, 2.99 mmol, 87% yield). m/z (ESI) 600.0 (M+H)+.

1. additioneach portion added over 5 min., 20-30 min apart)
2. customWith the reaction still at 0° C.
3. waitAfter 10 minutes
4. waitAfter for 30 min
5. customThe layers were separated
6. extractionthe aqueous layer was extracted again with 20 mL EtOAc
7. dry with materialThe combined organics were dried with sodium sulfate
8. filtrationfiltered
9. concentrationconcentrated
10. customto give a brown sticky solid, which
11. waitlet stand for 20 min
12. filtrationwas collected by filtration through a medium glass frit
13. washthe solid washed with iPrOH
14. customdried under high vac
15. concentrationThe filtrate was also concentrated to dryness
16. custompurified by Biotage, 100 g SNAP Ultra silica col
17. customonto dry column
18. custompurified with a gradient from 2-50% EtOAc/heptane
19. concentrationconcentrated under high vac

ORD record

ord-6c53facccdba477b916be497294591c2

Source dataset

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09212182B2