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

HRID 1468455Notes

Reaction equation

HRID 1468455 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]([Cl:23])[CH:11]=2)[CH:6]=1.[F:25][C:26]([F:38])([F:37])[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=1[S:33](Cl)(=[O:35])=[O:34].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:33]([C:28]3[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=3[C:26]([F:25])([F:37])[F:38])(=[O:35])=[O:34])=[CH:18][CH:17]=2)[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([Cl:23])[CH:11]=2)[CH:6]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 1366162-Trifluoromethylbenzenesulphonyl chlorideHCID 86694946[4-(4-Amino-phenyl)-6-chloro-3-methyl-naphthalen-2-yl]-acetic acid methyl ester

Product 1

HCID 86695032{6-Chloro-3-methyl-4-[4-(2-trifluoromethyl-benzenesulfonylamino)-phenyl]-naphthalen-2-yl}-acetic acid methyl esterYield 83.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of [4-(4-amino-phenyl)-6-chloro-3-methyl-naphthalen-2-yl]-acetic acid methyl ester (100 mg, 0.29 mmol) and 2-trifluoromethyl-benzenesulfonyl chloride (146 mg, 0.59 mmol) in THF (5.5 mL) was added diisopropylethylamine (0.15 mL, 0.85 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). Then, the organic compound was extracted into ethyl acetate (2×20 mL). The combined organic extracts were washed with brine solution (30 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 by using an ISCO (40 g) column chromatography eluting with 5-30% ethyl acetate in hexanes to afford {6-chloro-3-methyl-4-[4-(2-trifluoromethyl-benzenesulfonylamino)-phenyl]-naphthalen-2-yl}-acetic acid methyl ester (132 mg, 82%) as a light yellow foam. 1H NMR (300 MHz, DMSO-d6) δ ppm 10.80 (s, 1 H), 8.16 (d, J=7.2 Hz, 1 H), 8.03 (dd, J=7.2, 1.7 Hz, 1 H), 7.82-7.96 (m, 4 H), 7.45 (dd, J=8.8, 1.6 Hz, 1 H), 7.25 (d, J=8.5 Hz, 2 H), 7.12 (d, J=8.5 Hz, 2 H), 6.95 (d, J=1.6 Hz, 1 H), 3.92 (s, 2 H), 3.63 (s, 3 H), 1.98 (s, 3H). HRMS calcd. for C27H20ClF3NO4S [(M−H)−] 546.0759, obsd. 546.0762.

Workup

  1. additionAfter addition
  2. customThe solvent was removed under vacuum
  3. additionthe residue was diluted with water (10 mL)
  4. extractionThen, the organic compound was extracted into ethyl acetate (2×20 mL)
  5. washThe combined organic extracts were washed with brine solution (30 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 5-30% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-a017ac72073c4d5192b96e377e11eb6f
Source dataset
uspto-grants-2015_04
Patent number
US09000044B2

Reaction notes

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