Ammonium Chloride → N-[2-(4-Bromophenyl)thiophen-3-yl]propane-2-sulfonamide

Temperature

20 °C

Charge a double jacketed 20 L reactor equipped with mechanical stirrer and set under inert atmosphere of argon with 2-(4-Bromo-phenyl)-thiophene-3-ylamine (562 g, 2.21 mol) and CH2Cl2 (9.435 L). Obtain a clear solution. Add DBU (1.999 L) and cool the mixture to 9.4° C. Add propane-2-sulfonyl chloride (0.616 g) in 20 minutes maintaining the temperature below 25° C. Stir the reaction mixture 22 h at 20° C. After completion of reaction, cool the reaction mixture to 11° C. and add an aqueous solution of satd. aq. NH4Cl (7.65 L) cooled at 10° C. in 5 minutes. Heat the mixture to 20° C. and separate the aqueous phase. Wash the organic layer with 2N HCl (5.12 L), evaporate to dryness and take the residue into ethyl alcohol (800 g) . Heat the mixture until complete dissolution at 70° C. Cool the solution to 41° C. and add water (1384 mL). Stir the suspension overnight at 22° C., filter and wash two times with 254 mL of a 1/1 EtOH/H2O mixture. Dry the resulting beige solid under vacuum at 26° C. for 4 days to give propane-2-sulfonic acid[2-(4-bromo-phenyl)-thiophene-3-yl]-amide (688 g, 1.9 mol). 1H NMR (250 MHz, CDCl3): 1.25(d,6 H, J=6.9 H), 3.16 (hept, 1 H, J=6.9 Hz), 7.28(pseudo s, 2 H), 7.33(d, 2 H, J=8.5 Hz), 7.6(d, 2 H, J=8.5 Hz)

1. additionCharge a double jacketed 20 L reactor
2. customequipped with mechanical stirrer
3. customObtain a clear solution
4. customAfter completion of reaction
5. temperaturecool the reaction mixture to 11° C.
6. additionadd an aqueous solution of satd
7. temperatureHeat the mixture to 20° C.
8. customseparate the aqueous phase
9. washWash the organic layer with 2N HCl (5.12 L)
10. customevaporate to dryness
11. temperatureHeat the mixture
12. dissolutionuntil complete dissolution at 70° C
13. temperatureCool the solution to 41° C.
14. additionadd water (1384 mL)
15. stirringStir the suspension overnight at 22° C.
16. filtrationfilter
17. washwash two times with 254 mL of a 1/1 EtOH/H2O mixture
18. customDry the resulting beige solid under vacuum at 26° C. for 4 days

ORD record

ord-e7eddffeba9246d5bae4437cf810b086

Source dataset

uspto-grants-2008_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07393868B2