Benzenesulfonyl chloride → HCID 68717509, compound

HRID 1159859Notes

Reaction equation

HRID 1159859 reaction equation
N1C2C=CC=C(C=O)C=2C=[CH:2]1.[H-].[Na+].C1(S(Cl)(=O)=O)C=CC=CC=1.[C:24]1([S:30]([N:33]2[C:41]3[CH:40]=[CH:39][CH:38]=[C:37]([CH:42]=[O:43])[C:36]=3[CH:35]=[CH:34]2)(=[O:32])=[O:31])[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.C[Mg+].[Br-]>CN(C=O)C.C1COCC1.C1(C)C=CC=CC=1.C1COCC1.CO.C(Cl)Cl>[C:24]1([S:30]([N:33]2[C:41]3[C:36](=[C:37]([CH:42]([OH:43])[CH3:2])[CH:38]=[CH:39][CH:40]=3)[CH:35]=[CH:34]2)(=[O:31])=[O:32])[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1

Participants

11

Reactant 5

HCID 7369Benzenesulfonyl chlorideHCID 24758Sodium hydrideHCID 333703Indole-4-carboxaldehydeHCID 10107997HCID 10107997, compoundHCID 178418689HCID 178418689, compound

Product 1

HCID 68717509HCID 68717509, compoundYield 81%

Reagents, catalysts & solvents 5

HCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 22635083Tetrahydrofuran tolueneSolvent

Conditions

Temperature
0 °C

Procedure

A solution of indole-4-carboxaldehyde (1.00 g, 6.89 mmol) in DMF (60 mL) under N2 was treated with NaH (95%; 20.7 mmol, 496 mg) at rt for 15 min. benzenesulfonyl chloride (972 μL, 7.58 mmol) was added and stirring continued for 1 min. it was cooled to 0° C. and quenched with H2O. The reaction mixture was extracted with EtOAc (3×), the combined org. phases washed with H2O (3×), brine and dried (Na2SO4). conc. in vacuo gave an orange glue (1.79 g), which was directly used in the Grignard addition. The solution of crude 1-(phenylsulfonyl)-1H-indole-4-carbaldehyde in THF (60 mL) was treated with MeMgBr (9.84 mL of a 1.4 M solution in Toluene/THF, 13.78 mmol) at rt for 20 min upon which another 9.84 mL (2 eq) of Grignard reagent were added and stirring continued for another 5 min. The reaction mixture was quenched with sat. NH4Cl, extracted with EtOAc (3×), the combined org. phases washed with brine, dried (Na2SO4) and the solvent removed in vacuo to give a yellow-brownish glue (2.21 g). The crude product was subjected to flash chromatography (SiO2, CH2Cl2:MeOH=100:1) to yield the title compound as a yellow/orange foam (1.687 g, 81% over 2 steps). MS (ESI+) for C16H15NO3S m/z 284 (M-OH)+.

Workup

  1. additionwas added
  2. customquenched with H2O
  3. extractionThe reaction mixture was extracted with EtOAc (3×)
  4. washphases washed with H2O (3×), brine
  5. dry with materialdried (Na2SO4)
  6. customconc. in vacuo gave an orange glue (1.79 g), which
  7. additionwas directly used in the Grignard addition
  8. additionwere added
  9. stirringstirring
  10. waitcontinued for another 5 min
  11. customThe reaction mixture was quenched with sat. NH4Cl
  12. extractionextracted with EtOAc (3×)
  13. washphases washed with brine
  14. dry with materialdried (Na2SO4)
  15. customthe solvent removed in vacuo
  16. customto give a yellow-brownish glue (2.21 g)

Sources & evidence

ORD record
ord-6b9a144dfad14672b3417b7ae301547a
Source dataset
uspto-grants-2010_10
Patent number
US07812017B2

Reaction notes

Loading…