4-Methoxybenzenesulfonyl chloride → N-(tetrahydro-2H-pyran-2-ylmethoxy)-4-methoxy-1-benzenesulfonamide

HRID 1166476Notes

Reaction equation

HRID 1166476 reaction equation
[O:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[CH2:7][O:8][N:9]1C(=O)C2C(=CC=CC=2)C1=O.NN.[CH3:22][O:23][C:24]1[CH:29]=[CH:28][C:27]([S:30](Cl)(=[O:32])=[O:31])=[CH:26][CH:25]=1.C(N(C(C)C)CC)(C)C>C1COCC1>[O:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[CH2:7][O:8][NH:9][S:30]([C:27]1[CH:26]=[CH:25][C:24]([O:23][CH3:22])=[CH:29][CH:28]=1)(=[O:32])=[O:31]

Participants

6

Reactant 4

HCID 74014-Methoxybenzenesulfonyl chlorideHCID 9321HydrazineHCID 81531DiisopropylethylamineHCID 151664392-(tetrahydro-2H-pyran-2-ylmethoxy)-1H-isoindole-1,3(2H)-dione

Product 1

HCID 22997089N-(tetrahydro-2H-pyran-2-ylmethoxy)-4-methoxy-1-benzenesulfonamideYield 7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

2-(tetrahydro-2H-pyran-2-ylmethoxy)-1H-isoindole-1,3(2H)-dione (6.8 mmol, 1.77 g) was combined with hydrazine (6.8 mmol, 0.21 mL) in anhydrous THF (15 mL) under nitrogen. The reaction immediately formed a white suspension and was allowed to stir at room temperature for 2 hours. The suspension was filtered directly into a flask containing 4-methoxybenzenesulfonyl chloride (6.8 mmol, 1.40 g) and diisopropylethylamine (8.1 mmol, 1.42 mL) was added. After stirring at room temperature for 24 hours, the reaction was concentrated to a yellow solid. The resulting solid was partitioned between ethyl acetate and 1N HCl, and the organic layer was separated and washed with a saturated aqueous solution of sodium bicarbonate and brine, and dried over magnesium sulfate. The crude product was concentrated to a yellow solid and purified by silica gel chromatography (2:1 hexanes/ethyl acetate). The purified product was combined with ether and filtered to remove the residual phthalimide-hydrazine biproduct. The final product was crystallized using hexanes and ethyl acetate to provide 141 mg (7%) of white crystals. Rf=0.3 (2:1 hexanes/ethyl acetate); H1-NMR (CDCl3): δ 7.83 (2H,d), 7.05 (1H,s), 6.97 (2H,d), 4.01-3.86 (3H,m), 3.86 (3H,s), 3.63-3.57 (1H,m), 3.42-3.36 (1H,m), 1.88-1.78 (1H,m), 1.59-1.43 (4H,m), 1.3-1.15 (1H,m).

Workup

  1. customThe reaction
  2. customimmediately formed a white suspension
  3. filtrationThe suspension was filtered directly into a flask
  4. additionwas added
  5. stirringAfter stirring at room temperature for 24 hours
  6. concentrationthe reaction was concentrated to a yellow solid
  7. customThe resulting solid was partitioned between ethyl acetate and 1N HCl
  8. customthe organic layer was separated
  9. washwashed with a saturated aqueous solution of sodium bicarbonate and brine
  10. dry with materialdried over magnesium sulfate
  11. concentrationThe crude product was concentrated to a yellow solid
  12. custompurified by silica gel chromatography (2:1 hexanes/ethyl acetate)
  13. filtrationfiltered
  14. customto remove the residual phthalimide-hydrazine biproduct
  15. customThe final product was crystallized

Sources & evidence

ORD record
ord-869dd4859aac4ed1b3cecc59ee4bd029
Source dataset
uspto-grants-2003_09
Patent number
US06613743B2

Reaction notes

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