反应详情

To a 5 ml Biotage microwave reaction tube was added 2,3-difluoro-5-(chlorosulfonyl)benzoic acid (100 mg, 0.390 mmol). To this was added 2 ml of THF followed with (0.08 ml, 0.818 mmol) 10M aqueous NaOH. To the resulting stirred mixture was added ethanamine (0.195 ml, 0.390 mmol) as a 2M solution in THF. The reaction mixture was heated with stirring to 110° C. for 1.1 minutes using a Biotage Initiator 8 microwave set for high absorbance. After reaction cooled to room temperature 6M aqueous HCl (0.150 ml, 0.896 mmol) was added with stirring. The water was removed from the mixture by adding excess anhydrous Na2SO4 and subsequent filtration. The filtered salts were washed with acetonitrile and DMF (19:1, 10 ml, 2×). The combined filtrates were concentrated with rotary evaporation, yielding a DMF solution of 5-[(ethylamino)sulfonyl]-2,3-difluorobenzoic acid (82% pure by LCMS, % purity used as stoichiometry for next step), which was carried forward without purification.

1. customTo a 5 ml Biotage microwave reaction tube
2. temperatureThe reaction mixture was heated
3. stirringwith stirring to 110° C. for 1.1 minutes
4. customAfter reaction
5. additionwas added
6. stirringwith stirring
7. customThe water was removed from the mixture
8. additionby adding excess
9. filtrationanhydrous Na2SO4 and subsequent filtration
10. washThe filtered salts were washed with acetonitrile and DMF (19:1, 10 ml, 2×)
11. concentrationThe combined filtrates were concentrated with rotary evaporation