4-Methoxybenzenesulfonyl chloride → N-(isopropoxy)-4-methoxy-1-benzenesulfonamide

HRID 29150Notes

Reaction equation

HRID 29150 reaction equation
[CH:1]([O:4][N:5]1C(=O)C2C(=CC=CC=2)C1=O)([CH3:3])[CH3:2].NN.[CH3:18][O:19][C:20]1[CH:25]=[CH:24][C:23]([S:26](Cl)(=[O:28])=[O:27])=[CH:22][CH:21]=1.C(N(CC)C(C)C)(C)C>O1CCCC1.ClCCl>[CH:1]([O:4][NH:5][S:26]([C:23]1[CH:24]=[CH:25][C:20]([O:19][CH3:18])=[CH:21][CH:22]=1)(=[O:28])=[O:27])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 74014-Methoxybenzenesulfonyl chlorideHCID 9321HydrazineHCID 81531DiisopropylethylamineHCID 27689132-(1-Methylethoxy)-1H-isoindole-1,3(2H)-dione

Product 1

HCID 22997078N-(isopropoxy)-4-methoxy-1-benzenesulfonamideYield 69%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A vigorously stirred solution of 2-isopropoxy-1H-isoindole-1,3(2H)-dione [2.50 g, 12.2 mmol, Synth. Comm., 22(10), 1427-1432 (1992)] in 35 mL of tetrahydrofuran under an Argon atmosphere at ambient temperature was treated with anhydrous hydrazine (0.421 mL, 13.41 mmol). After 1.5 hours, 4-methoxybenzenesulphonyl chloride (3.024 g, 14.63 mmol), dichloromethane (20 mL) and N,N-diisopropylethylamine (6.38 mL, 36.6 mmol) was added with continued stirring. After an additional 2 hours at ambient temperature, the reaction mixture was evaporated in vacuo to a residue and partitioned between ethyl acetate and 1N hydrochloric acid. The layers were separated and the aqueous layer was extracted again with ethyl acetate. The combined organic layers were washed with 5% w/v potassium carbonate and brine, dried over anhydrous magnesium sulfate, filtered and evaporated in vacuo to a residue. The crude material was purified on Flash grade silica gel eluting with 30% ethyl acetate in hexane. Fractions containing the product were combined, evaporated in vacuo, and dried under high vacuum to provide N1-(isopropoxy)-4-methoxy-1-benzenesulfonamide (2.061 g, 69%) as a white solid. H1-NMR (chloroform-D3): 1.22 (d, 6H), 3.92 (s, 3H), 4.27 (m, 1H), 6.70 (s, 1H), 7.05 (d, 2H), 7.90 (d, 2H). MS(ESI): 268 (M+Na).

Workup

  1. waitAfter an additional 2 hours at ambient temperature
  2. customthe reaction mixture was evaporated in vacuo to a residue
  3. custompartitioned between ethyl acetate and 1N hydrochloric acid
  4. customThe layers were separated
  5. extractionthe aqueous layer was extracted again with ethyl acetate
  6. washThe combined organic layers were washed with 5% w/v potassium carbonate and brine
  7. dry with materialdried over anhydrous magnesium sulfate
  8. filtrationfiltered
  9. customevaporated in vacuo to a residue
  10. customThe crude material was purified on Flash grade silica gel eluting with 30% ethyl acetate in hexane
  11. additionFractions containing the product
  12. customevaporated in vacuo
  13. customdried under high vacuum

Sources & evidence

ORD record
ord-71ef0007f0db434fa3c95d0f6b01b997
Source dataset
uspto-grants-2008_09
Patent number
US07419967B2

Reaction notes

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