4-Toluenesulfonyl chloride → HCID 58886489, compound

HRID 425896Notes

Reaction equation

HRID 425896 reaction equation
[CH3:1][O:2][C:3](=[O:18])[C:4]1[CH:9]=[CH:8][C:7]([C:10]2[CH:11]=[N:12][C:13]([NH2:17])=[C:14]([OH:16])[CH:15]=2)=[CH:6][CH:5]=1.C(N(CC)C(C)C)(C)C.[CH3:28][C:29]1[CH:34]=[CH:33][C:32]([S:35](Cl)(=[O:37])=[O:36])=[CH:31][CH:30]=1>C(Cl)Cl.CN(C1C=CN=CC=1)C>[CH3:1][O:2][C:3](=[O:18])[C:4]1[CH:5]=[CH:6][C:7]([C:10]2[CH:11]=[N:12][C:13]([NH2:17])=[C:14]([O:16][S:35]([C:32]3[CH:33]=[CH:34][C:29]([CH3:28])=[CH:30][CH:31]=3)(=[O:37])=[O:36])[CH:15]=2)=[CH:8][CH:9]=1

Participants

6

Reactant 3

HCID 73974-Toluenesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 58886610HCID 58886610, compound

Product 1

HCID 58886489HCID 58886489, compoundYield 88.2%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a stirring solution of 4-(6-amino-5-hydroxy-pyridin-3-yl)-benzoic acid methyl ester (2.3 g, 9.3 mmol) in CH2Cl2 (180 mL) was added N,N-diisopropylethylamine (3.2 mL, 0.019 mol), 4-methyl-benzenesulfonyl chloride (2.66 g, 0.014 mol), and PS-DMAP (catalytic amount). The reaction was stirred at ambient temperature for 6 hr then filtered to remove the resin. The resin was washed with CH2Cl2 (3×20 mL), and the combined fractions were washed with 10% citric acid (100 mL), saturated NaCl (100 mL), dried (Na2SO4) and filtered and concentrated in vacuo. The resulting crude material was purified by column chromatography (silica gel, 100% CH2Cl2 to 95:5 CH2Cl2:MeOH) and the fractions containing the desired product were combined and concentrated in vacuo to yield 4-[6-Amino-5-(toluene-4-sulfonyloxy)-pyridin-3-yl]-benzoic acid methyl ester (3.3 g, 8.2 mmol, 88%). 1H NMR (CDCl3, 300 MHz) δ 2.47 (s, 3H), 3.93 (s, 3H), 4.81-4.88 (brs, 2H), 7.36-7.44 (m, 5H), 7.81 (d, 2H, J, 8.3 Hz), 8.05 (d, 2H, J, 8.4 Hz), 8.19-8.27 (brs, 1H).

Workup

  1. filtrationthen filtered
  2. customto remove the resin
  3. washThe resin was washed with CH2Cl2 (3×20 mL)
  4. washthe combined fractions were washed with 10% citric acid (100 mL), saturated NaCl (100 mL)
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe resulting crude material was purified by column chromatography (silica gel, 100% CH2Cl2 to 95:5 CH2Cl2:MeOH)
  9. additionthe fractions containing the desired product
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-428a5b3feea0450db428b236311fc178
Source dataset
uspto-grants-2012_01
Patent number
US08106197B2

Reaction notes

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