1,2-Dichloroethane → HCID 57884061, compound

To a flask containing 2-iodo-4-trifluoromethylaniline (5.66 g, 19.7 mmol) were added pyruvic acid (4.17 mL, 59.2 mmol), DABCO (6.68 g, 59.2 mmol), magnesium sulfate (3.56 g, 29.6 mmol), and palladium acetate (443 mg, 1.97 mmol). The mixture was purged with N2 and dry DMF (60 mL) was added. The resultant suspension was deoxygenated via N2-sparge for 15 min, then was capped and placed in a 105° C. bath. After 48 h, the mixture was allowed to cool to room temperature. The insoluble materials were filtered and the filtrate was diluted with EtOAc. The organic phase was washed (H2O, then 1 N HCl), dried over anhydrous Na2SO4, and concentrated in vacuo: LCMS E, tr=2.95 min, m/z 228.1 [M−H]. To a flask containing the crude product obtained above were added EDC (8.0 g, 42.0 mmol), HOBt (5.67 g, 42.0 mmol) and N,O-dimethylhydroxylamine hydrochloride (4.10 g, 42.0 mmol). The resultant mixture was dissolved in DMF (30 mL), DIEA (11.8 mL, 67 mmol) was added, and the reaction mixture was stirred at 50° C. for 18 h. The mixture was then allowed to cool to room temperature and was quenched by pouring into sat. aq. NaHCO3. The aqueous phase was extracted with EtOAc (2×) and the combined organic phases were concentrated in vacuo. Purification by flash chromatography on silica gel (20 to 40%, then 40 to 100% EtOAc in hexanes) provided the title compound: LCMS B, tr=2.08 min, m/z 273.1 [M+H]+. 1H NMR (500 MHz, CDCl3) δ 9.67 (br s, 1H), 8.02 (s, 1H), 7.52 (d, J=1.0 Hz, 2H), 7.31 (d, J=2.0 Hz, 1H), 3.86 (s, 3H), 3.46 (s, 3H).

1. customThe mixture was purged with N2 and dry DMF (60 mL)
2. additionwas added
3. customThe resultant suspension was deoxygenated via N2-
4. customsparge for 15 min
5. customwas capped
6. customplaced in a 105° C.
7. filtrationThe insoluble materials were filtered
8. additionthe filtrate was diluted with EtOAc
9. washThe organic phase was washed (H2O
10. dry with material1 N HCl), dried over anhydrous Na2SO4
11. concentrationconcentrated in vacuo
12. customLCMS E, tr=2.95 min, m/z 228.1 [M−H]
13. additionTo a flask containing the crude product
14. customobtained above
15. temperatureto cool to room temperature
16. customwas quenched
17. additionby pouring into sat. aq. NaHCO3
18. extractionThe aqueous phase was extracted with EtOAc (2×)
19. concentrationthe combined organic phases were concentrated in vacuo
20. customPurification by flash chromatography on silica gel (20 to 40%

ORD record

ord-4574c0007a7b4e53b0e0a38f6bb2caa0

Source dataset

uspto-grants-2009_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07598398B2