Reaction #471705

Reaction equation

2-chloro-benzothiazole

2-fluoro-4-hydroxy-benzoic acid

Cs2CO3

→

title compound

Yield 63.5%

4-(Benzothiazol-2-yloxy)-2-fluoro-benzoic acid

Yield 63.5%

Solvents

DMF

Conditions

Workup

1. 1
   workup.STIRRINGThe reaction mixture was stirred at 100° C. for 50 h
2. 2
   Temperaturecooled to rt
3. 3
   Filtrationthe solid was filtered
4. 4
   workup.ADDITIONThe filtrate was diluted with EtOAc (200 mL) and water (100 mL)
5. 5
   Otherthe organic layer was separated
6. 6
   ExtractionThe aqueous layer was extracted with EtOAc (2×200 mL)
7. 7
   Dryingdried (Na2SO4)
8. 8
   Filtrationfiltered
9. 9
   Concentrationconcentrated

Procedure

A solution of 2-fluoro-4-hydroxy-benzoic acid (4.0 g, 25.6 mmol) in DMF (250 mL) was added Cs2CO3 (9.2 g, 28.2 mmol) and the reaction mixture was stirred at 80° C. for 1 h prior to the addition of 2-chloro-benzothiazole (3.3 mL, 25.6 mmol). The reaction mixture was stirred at 100° C. for 50 h, then cooled to rt, and the solid was filtered. The filtrate was diluted with EtOAc (200 mL) and water (100 mL), neutralized with 1 M HCl and the organic layer was separated. The aqueous layer was extracted with EtOAc (2×200 mL). The organic layers were combined, dried (Na2SO4), filtered, and concentrated to afford the title compound as a colorless solid (4.7 g, 63%). MS (ESI): mass calcd. for C14H8FNO3S, 289.0; m/z found, 290.1 [M+H]+. 1H NMR (400 MHz, CD3OD): 8.21 (t, J=8.5 Hz, 1H), 7.99 (d, J=8.5 Hz, 1H), 7.87 (d, J=8.11 Hz, 1H), 7.63-7.45 (m, 4H).

Source