Triethylamine → 2,6-Difluoro-3-(n-(propylsulfonyl)propyl-sulfonamido)benzoic acid

HRID 2196631Notes

Reaction equation

HRID 2196631 reaction equation
[CH2:1]([S:4](Cl)(=[O:6])=[O:5])[CH2:2][CH3:3].[NH2:8][C:9]1[C:10]([F:19])=[C:11]([C:15]([F:18])=[CH:16][CH:17]=1)[C:12]([OH:14])=[O:13].C(N([CH2:25][CH3:26])CC)C>C(Cl)Cl>[F:19][C:10]1[C:9]([N:8]([S:4]([CH2:1][CH2:25][CH3:26])(=[O:6])=[O:5])[S:4]([CH2:1][CH2:2][CH3:3])(=[O:6])=[O:5])=[CH:17][CH:16]=[C:15]([F:18])[C:11]=1[C:12]([OH:14])=[O:13]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 662791-Propanesulfonyl chlorideHCID 184053523-Amino-2,6-difluorobenzoic acid

Product 1

HCID 580953482,6-Difluoro-3-(n-(propylsulfonyl)propyl-sulfonamido)benzoic acidYield 74.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-92af102a70b34abbacfbf99b226169d2
Source dataset
uspto-grants-2012_12
Patent number
US08338452B2

Reaction notes

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