Chlorosulfonic acid → 5-[(1,3-Dioxoisoindol-2-yl)methyl]thiophene-2-sulfonyl chloride

HRID 735834Notes

Reaction equation

HRID 735834 reaction equation
[S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[CH2:6][N:7]1[C:15](=[O:16])[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[C:8]1=[O:17].[Cl:18][S:19](O)(=[O:21])=[O:20]>C(Cl)Cl>[O:16]=[C:15]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[C:8](=[O:17])[N:7]1[CH2:6][C:2]1[S:1][C:5]([S:19]([Cl:18])(=[O:21])=[O:20])=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 24638Chlorosulfonic acidHCID 33541542-(Thiophen-2-ylmethyl)isoindoline-1,3-dione

Product 1

HCID 178101595-[(1,3-Dioxoisoindol-2-yl)methyl]thiophene-2-sulfonyl chlorideYield 67.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a cold (−78° C.) solution of 2-(thien-2-ylmethyl)-1H-isoindole-1,3(2H)-dione (6.78 g, 27.87 mmol) in DCM (56 mL) was added dropwise (in about 10 min) chlorosulfonic acid (16.237 g, 139.3 mmol, 9.33 mL, d: 1.74) diluted in DCM (9.3 mL). The reaction mixture was stirred 2 h at −78° C., then 1 h at −40° C. and overnight at rt. The resulting brown solution was poured on ice. The mixture was extracted with DCM (3×200 mL), and the combined organic layers were washed with water (3×200 mL), dried over MgSO4, filtered and concentrated to afford a yellowish oil. This crude product was purified by column chromatography over silica gel (AcOEt/c-Hex 1/4 to 1/3 to 1/2 in about 1 h) to give the title compound as a white solid (6.42 g, 67%). 1H NMR (CDCl3, 300 MHz) δ 7.89 (d, 1H. J=5.5 Hz), 7.87 (d, 1H. J=5.5 Hz), 7.76 (d, 1H, J=5.5 Hz), 7.75 (d, 1H, J=5.5 Hz), 7.71 (d, 1H, J=4.0 Hz), 7.18 (d, 1H, J=4.0 Hz), 5.05 (s, 2H). HPLC (Condition A), Rt: 4.6 min (HPLC purity: 94.8%).

Workup

  1. custom1 h
  2. customat −40° C.
  3. customovernight
  4. customat rt
  5. additionThe resulting brown solution was poured on ice
  6. extractionThe mixture was extracted with DCM (3×200 mL)
  7. washthe combined organic layers were washed with water (3×200 mL)
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customto afford a yellowish oil
  12. customThis crude product was purified by column chromatography over silica gel (AcOEt/c-Hex 1/4 to 1/3 to 1/2 in about 1 h)

Sources & evidence

ORD record
ord-5720772572f544799b24808883291402
Source dataset
uspto-grants-2009_09
Patent number
US07592477B2

Reaction notes

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