Trifluoroacetic acid → HCID 69689575, compound

Temperature

-78 °C

1-(3-Fluoro-4-methoxyphenyl)-2-(4-aminosulfonylphenyl-ethan-1-one oxime from Step 3 (2.0 g, 5.9 mmol), and triethylamine (0.60 g, 5.9 mmol) were dissolved in tetrahydrofuran (100 mL) and treated with bis(1,2-chlorodimethylsilyl)ethane (1.27 g, 5.9 mmol) at room temperature. After 15 minutes, the solution was cooled to -78° C. and lithium diisopropylamide (2.0M solution in heptane/tetrahydrofuran/ethylbenzene, 7.75 mL, 19.5 mmol) was added dropwise. The solution was warmed to -15° C., and ethyl difluoroacetate (0.89 g, 6.5 mmol) was added. After stirring 0.5 hour, trifluoroacetic acid (40 mL) and water (10 mL) were added. The resulting dark mixture was heated to reflux for 20 hours, concentrated, dissolved in ethyl acetate (100 mL), washed with brine, saturated aqueous NaHCO3, and water, dried over MgSO4, and concentrated. A dark oily solid was crystallized from ethyl acetate/hexane to give a white solid (0.3 g, 13%): mp 188.2°-190.0° C. 1H NMR (acetone-d6 /300 MHz) 8.0 (d, J=8.4 Hz, 2H), 7.6 (d, J=8.7 Hz, 2H), 7.2 (m, 3H), 7.1 (t, J=51.9 Hz, 1H), 6.7 (bs, 2H), 3.9 (s, 3H). Anal. Calc'd. for C17H13F3N2O4S: C, 51.26; H. 3.29; N, 7.03. Found: C, 51.35; H, 3.33; N, 6.89.

1. temperatureThe solution was warmed to -15° C.
2. temperatureThe resulting dark mixture was heated
3. temperatureto reflux for 20 hours
4. concentrationconcentrated
5. dissolutiondissolved in ethyl acetate (100 mL)
6. washwashed with brine, saturated aqueous NaHCO3, and water
7. dry with materialdried over MgSO4
8. concentrationconcentrated
9. customA dark oily solid was crystallized from ethyl acetate/hexane

ORD record

ord-53233a33b6084ff59f65f07f851a97bf

Source dataset

uspto-grants-1999_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05859257