o-Toluenesulfonyl chloride → {6-Chloro-3-methyl-4-[4-(toluene-2-sulfonylamino)-phenyl]-naphthalen-2-yl}-acetic acid methyl ester

HRID 1468457Notes

Reaction equation

HRID 1468457 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.[CH3:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=1[S:32](Cl)(=[O:34])=[O:33].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:32]([C:27]3[C:26]([CH3:25])=[CH:31][CH:30]=[CH:29][CH:28]=3)(=[O:34])=[O:33])=[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 8623o-Toluenesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 86694946[4-(4-Amino-phenyl)-6-chloro-3-methyl-naphthalen-2-yl]-acetic acid methyl ester

Product 1

HCID 86695033{6-Chloro-3-methyl-4-[4-(toluene-2-sulfonylamino)-phenyl]-naphthalen-2-yl}-acetic acid methyl esterYield 62.8%

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-Methyl-benzenesulfonyl chloride (113 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. The residue was diluted with water (10 mL) and the mixture was extracted with 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 using an ISCO (40 g) column, eluting with 5-30% ethyl acetate in hexanes, to afford {6-chloro-3-methyl-4-[4-(toluene-2-sulfonylamino)-phenyl]-naphthalen-2-yl}-acetic acid methyl ester (90 mg, 62.1%) as a white foam. HRMS calcd. for C27H23ClFNO4S [(M−H)−] 492.1042, obsd. 492.1042.

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 (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-b1158c1c22504622b4eb82f194edf2eb
Source dataset
uspto-grants-2015_04
Patent number
US09000044B2

Reaction notes

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