Diisopropylethylamine → {4-[4-(3,5-Bis-trifluoromethyl-benzenesulfonylamino)-phenyl]-6-fluoro-3-methyl-naphthalen-2-yl}-acetic acid methyl ester

HRID 1468452Notes

Reaction equation

HRID 1468452 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.[F:25][C:26]([F:42])([F:41])[C:27]1[CH:28]=[C:29]([S:37](Cl)(=[O:39])=[O:38])[CH:30]=[C:31]([C:33]([F:36])([F:35])[F:34])[CH:32]=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:37]([C:29]3[CH:30]=[C:31]([C:33]([F:34])([F:35])[F:36])[CH:32]=[C:27]([C:26]([F:25])([F:41])[F:42])[CH:28]=3)(=[O:39])=[O:38])=[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 81531DiisopropylethylamineHCID 5209453,5-Bis(trifluoromethyl)benzenesulphonyl chlorideHCID 86694944[4-(4-Amino-phenyl)-6-fluoro-3-methyl-naphthalen-2-yl]-acetic acid methyl ester

Product 1

HCID 86695030{4-[4-(3,5-Bis-trifluoromethyl-benzenesulfonylamino)-phenyl]-6-fluoro-3-methyl-naphthalen-2-yl}-acetic acid methyl esterYield 21.1%

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 3,5-bis(trifluoromethyl)benzenesulfonyl chloride (54 mg, 0.17 mmol) in THF (3 mL) was added diisopropylethylamine (62 mg, 0.48 mmol) at 0° C. under nitrogen. After addition, 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 (20 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-(3,5-bis-trifluoromethyl-benzenesulfonylamino)-phenyl]-6-fluoro-3-methyl-naphthalen-2-yl}-acetic acid methyl ester (21.5 mg, 21%) as a light brown solid. 1H NMR (300 MHz, CDCl3) δ ppm 8.23 (s, 2 H), 8.09 (s, 1 H), 7.78 (dd, J=8.8, 5.7 Hz, 1 H), 7.73 (s, 1 H), 7.11-7.24 (m, 5 H), 7.04 (s, 1 H), 6.73 (d, J=10.9 Hz, 1 H), 3.87 (s, 2 H), 3.75 (s, 3 H), 2.07 (s, 3 H). HRMS calcd. for C28H19F7NO4S [(M−H)−] 598.0928, obsd. 598.0925.

Workup

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

Sources & evidence

ORD record
ord-07226840cd20458f86e3c0c6408ef4e2
Source dataset
uspto-grants-2015_04
Patent number
US09000044B2

Reaction notes

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