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0 °C

Propane-1-sulfonyl chloride (1.225 mL, 10.92 mmol) was added to a mixture of 3-amino-2,6-difluorobenzoic acid (0.573 g, 3.310 mmol), triethylamine (2.030 mL, 14.56 mmol) and CH2Cl2 (17 mL, 0.2M) cooled to 0° C. The reaction mixture was allowed to warm to room temperature and stirred for 1 hour. The mixture was then partitioned between saturated NaHCO3 (100 mL) and ethyl acetate (75 mL). The aqueous layer was washed with ethyl acetate (50 mL) and then acidified with concentrated HCl to a pH of about 1. The acidified aqueous layer was extracted with ethyl acetate (2×50 mL), and the combined ethyl acetate extracts were dried (Na2SO4), filtered and concentrated. The resulting residue was triturated with hexanes to afford 2,6-difluoro-3-(N-(propylsulfonyl)propyl-sulfonamido)benzoic acid as a solid (0.948 g, 74% yield). 1H NMR (400 MHz, d6-DMSO) δ 7.90-7.84 (m, 1H), 7.39-7.34 (m, 1H), 3.73-3.58 (m, 4H), 1.88-1.74 (m, 4H), 1.01 (t, J=7.5 Hz, 6H). m/z (APCI-neg) M-(SO2Pr)=278.1.

1. temperatureto warm to room temperature
2. customThe mixture was then partitioned between saturated NaHCO3 (100 mL) and ethyl acetate (75 mL)
3. washThe aqueous layer was washed with ethyl acetate (50 mL)
4. extractionThe acidified aqueous layer was extracted with ethyl acetate (2×50 mL)
5. dry with materialthe combined ethyl acetate extracts were dried (Na2SO4)
6. filtrationfiltered
7. concentrationconcentrated
8. customThe resulting residue was triturated with hexanes