Triethylamine → HCID 17859128, compound

Temperature

0 °C

3-Fluorobenzenethiol (5.0 g, 39.0 mmol) was dissolved in methylene chloride (200 ml), and oxalyl chloride (3.57 ml, 41.0 mmol) and triethylamine (5.71 ml, 41.0 mmol) were added to the solution under stirring at 0° C. The reaction mixture was stirred for 24 hours at room temperature. The reaction mixture was distilled under reduced pressure to remove the solvent. The residue was suspended in methylene chloride (100 ml). After aluminum chloride (7.8 g, 58.5 mmol) was added to the reaction mixture under cooling at 0° C., the reaction mixture was stirred at room temperature for 4 hours. The reaction mixture was poured in ice water, followed by extraction with chloroform. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate and distilled under reduced pressure to remove the solvent. To the residue were added concentrated aqueous ammonia (28%, 50 ml) and hydrogen peroxide (35% in water, 50 ml) and the mixture was stirred at room temperature for 24 hours. The crystals thus precipitated were collected by filtration and added with THF (100 ml) and 0.25M NaOH (60 ml, 15 mmol). The resulting mixture was heated under reflux for 24 hours. The reaction mixture was cooled to room temperature and poured in 1M HCl. The mixture was concentrated to dryness under reduced pressure. The residue was purified with chromatography on a silica gel column (middle pressure chromatography system Yamazen, C-18 column, linear gradient of H20 (0.1% HCOOH) and methanol (0.1% HCOOC) from 10% to 90%, 10 ml/min) to give 4-fluorobenzo(d)isothiazole-3-carboxylic acid (590 mg, 8%) as a colorless solid.

1. stirringThe reaction mixture was stirred for 24 hours at room temperature
2. distillationThe reaction mixture was distilled under reduced pressure
3. customto remove the solvent
4. temperatureunder cooling at 0° C.
5. stirringthe reaction mixture was stirred at room temperature for 4 hours
6. extractionfollowed by extraction with chloroform
7. washThe extract was washed with saturated brine
8. dry with materialdried over anhydrous magnesium sulfate
9. distillationdistilled under reduced pressure
10. customto remove the solvent
11. additionTo the residue were added concentrated aqueous ammonia (28%, 50 ml) and hydrogen peroxide (35% in water, 50 ml)
12. stirringthe mixture was stirred at room temperature for 24 hours
13. customThe crystals thus precipitated
14. filtrationwere collected by filtration
15. temperatureThe resulting mixture was heated
16. temperatureunder reflux for 24 hours
17. temperatureThe reaction mixture was cooled to room temperature
18. concentrationThe mixture was concentrated to dryness under reduced pressure
19. customThe residue was purified with chromatography on a silica gel column (middle pressure chromatography system Yamazen, C-18 column, linear gradient of H20 (0.1% HCOOH) and methanol (0.1% HCOOC) from 10% to 90%, 10 ml/min)

ORD record

ord-ea234098cd0e4cf59dae8cae05f70bea

Source dataset

uspto-grants-2007_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07157487B2