Benzenesulfonyl chloride → [4-(4-Benzenesulfonylamino-phenyl)-6-fluoro-3-methyl-naphthalen-2-yl]-acetic acid methyl ester

HRID 1468450Notes

Reaction equation

HRID 1468450 reaction equation
[CH3:1][O:2][C:3](=[O:24])[CH2:4][C:5]1[C:14]([CH3:15])=[C:13]([C:16]2[CH:21]=[CH:20][C:19]([NH2:22])=[CH:18][CH:17]=2)[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([F:23])[CH:11]=2)[CH:6]=1.[C:25]1([S:31](Cl)(=[O:33])=[O:32])[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.C(N(C(C)C)CC)(C)C>C1COCC1>[CH3:1][O:2][C:3](=[O:24])[CH2:4][C:5]1[C:14]([CH3:15])=[C:13]([C:16]2[CH:21]=[CH:20][C:19]([NH:22][S:31]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)(=[O:33])=[O:32])=[CH:18][CH:17]=2)[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([F:23])[CH:11]=2)[CH:6]=1

Participants

5

Reactant 3

HCID 7369Benzenesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 86694944[4-(4-Amino-phenyl)-6-fluoro-3-methyl-naphthalen-2-yl]-acetic acid methyl ester

Product 1

HCID 86695029[4-(4-Benzenesulfonylamino-phenyl)-6-fluoro-3-methyl-naphthalen-2-yl]-acetic acid methyl esterYield 48.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of [4-(4-amino-phenyl)-6-fluoro-3-methyl-naphthalen-2-yl]-acetic acid methyl ester (55 mg, 0.17 mmol) and benzenesulfonyl chloride (61 mg, 0.34 mmol) in THF (3 mL) was added diisopropylethylamine (62 mg, 0.49 mmol) at 0° C. under nitrogen. The reaction mixture was warmed to room temperature and stirred for 3 hours. The solvent was removed under vacuum and the residue was diluted with water (10 mL). The mixture was extracted with ethyl acetate (2×20 mL). The combined organic extracts were washed with brine solution (50 mL) and dried over anhydrous magnesium sulfate. Filtration of the drying agent and concentration of the solvent under vacuum gave the crude residue which was purified using an ISCO (12 g) column, eluting with 2-25% ethyl acetate in hexanes, to afford [4-(4-benzenesulfonylamino-phenyl)-6-fluoro-3-methyl-naphthalen-2-yl]-acetic acid methyl ester (38 mg, 48%) as a white solid. 1H NMR (300 MHz, CDCl3) δ ppm 7.84 (d, J=7.5 Hz, 2 H), 7.77 (dd, J=9.1, 6.0 Hz, 1 H), 7.70 (s, 1 H), 7.59 (t, J=7.5 Hz, 1 H), 7.49 (t, J=7.5 Hz, 2 H), 7.15-7.22 (m, 3 H), 7.10 (d, J=8.2 Hz, 2 H), 6.80 (s, 1 H), 6.71 (dd, J=11.3, 2.3 Hz, 1 H), 3.78-3.90 (m, 2 H), 3.73 (s, 3 H), 2.09 (s, 3 H). HRMS calcd. for C26H21FNO4S [(M−H)−] 462.1181, obsd. 462.1179.

Workup

  1. customThe solvent was removed under vacuum
  2. additionthe residue was diluted with water (10 mL)
  3. extractionThe mixture was extracted with ethyl acetate (2×20 mL)
  4. washThe combined organic extracts were washed with brine solution (50 mL)
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationFiltration of the drying agent and concentration of the solvent under vacuum
  7. customgave the crude residue which
  8. customwas purified
  9. washeluting with 2-25% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-ea825415ceb7466da700792977800bd1
Source dataset
uspto-grants-2015_04
Patent number
US09000044B2

Reaction notes

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