Phosphorus pentachloride → 3-(1,3-dioxo-2,3-dihydro-1H-isoindol-2-yl)propane-1-sulfonyl chloride

HRID 1919404Notes

Reaction equation

HRID 1919404 reaction equation
[O:1]=[C:2]1[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[C:4](=[O:11])[N:3]1[CH2:12][CH2:13][CH2:14][S:15]([O-:18])(=O)=[O:16].[K+].P(Cl)(Cl)(Cl)(Cl)[Cl:21]>ClCCl>[Cl:21][S:15]([CH2:14][CH2:13][CH2:12][N:3]1[C:2](=[O:1])[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[C:4]1=[O:11])(=[O:18])=[O:16]

Participants

4

Reactant 2

HCID 24819Phosphorus pentachlorideHCID 23707812HCID 23707812, compound

Product 1

HCID 154532703-(1,3-dioxo-2,3-dihydro-1H-isoindol-2-yl)propane-1-sulfonyl chlorideYield 35%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Adapting a procedure according to Shue et al., Bioorg. Med. Chem. 1996, 6, 1709-1714, a 250 mL round-bottomed flask equipped with a magnetic stirring bar and a reflux condenser was charged under an atmosphere of nitrogen with 5.4 g (20 mmol) of potassium 3-(1,3-dioxobenzo[c]azolin-2-yl)propanesulfonic acid (10a), 150 mL of anhydrous dichloromethane (DCM), and 4.6 g (22 mmol) of phosphorus pentachloride (PCl5). The reaction mixture was heated to reflux. After reacting overnight, the reaction mixture was quenched with water and the phases were separated. The aqueous phase was extracted with dichloromethane (DCM). The combined organic extracts were washed with brine, dried over anhydrous magnesium sulfate (MgSO4), filtered, and the solvents removed under reduced pressure using a rotary evaporator. After work-up, the crude material was purified by silica gel column chromatography using a mixture of ethyl acetate (EtOAc) and hexane (Hxn) (EtOAc/Hxn=1:2) as eluent to provide 2.0 g (35% yield) of the title compound (10) as an off-white to beige solid. 1H NMR (400 MHz, CDCl3): δ=2.42-2.49 (m, 2H), 3.75-3.79 (m, 2H), 3.91 (t, J=6.4 Hz, 2H), 7.75-7.77 (m, 2H), 7.87-7.89 (m, 2H) ppm. MS (ESI) m/z 287.99 (M+H)+. The analytical data was consistent the proposed structure.

Workup

  1. custom1996, 6, 1709-1714, a 250 mL round-bottomed flask equipped with a magnetic stirring bar and a reflux condenser
  2. temperatureThe reaction mixture was heated to reflux
  3. customthe reaction mixture was quenched with water
  4. customthe phases were separated
  5. extractionThe aqueous phase was extracted with dichloromethane (DCM)
  6. washThe combined organic extracts were washed with brine
  7. dry with materialdried over anhydrous magnesium sulfate (MgSO4)
  8. filtrationfiltered
  9. customthe solvents removed under reduced pressure
  10. customa rotary evaporator
  11. customAfter work-up, the crude material was purified by silica gel column chromatography
  12. additiona mixture of ethyl acetate (EtOAc) and hexane (Hxn) (EtOAc/Hxn=1:2) as eluent

Sources & evidence

ORD record
ord-9707e110cd1246ceba635a2f6f554c29
Source dataset
uspto-grants-2012_05
Patent number
US08168617B2

Reaction notes

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