4-Toluenesulfonyl chloride → HCID 54058252, compound

HRID 1432868Notes

Reaction equation

HRID 1432868 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:13]=[C:12]2[C:8]([C:9]([Cl:14])=[CH:10][NH:11]2)=[CH:7][CH:6]=1)=[O:4].[Li+].CC([N-]C(C)C)C.[C:23]1([CH3:33])[CH:28]=[CH:27][C:26]([S:29](Cl)(=[O:31])=[O:30])=[CH:25][CH:24]=1>C1COCC1>[CH3:1][O:2][C:3]([C:5]1[CH:13]=[C:12]2[C:8]([C:9]([Cl:14])=[CH:10][N:11]2[S:29]([C:26]2[CH:27]=[CH:28][C:23]([CH3:33])=[CH:24][CH:25]=2)(=[O:31])=[O:30])=[CH:7][CH:6]=1)=[O:4]

Participants

5

Reactant 3

HCID 73974-Toluenesulfonyl chlorideHCID 2724682Lithium diisopropylamideHCID 13930510HCID 13930510, compound

Product 1

HCID 54058252HCID 54058252, compoundYield 58.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of 3-chloro-1H-indole-6-carboxylic acid methyl ester (3.00 g, 17.1 mmol) in 40 mL of THF at −78° C. is added LDA(8.55 mL of a 2.0M solution in hexanes, 17.1 mmol) dropwise. The solution is stirred at −78° C. for 30 minutes p-Toluenesulfonyl chloride (3.43 g, 18.0 mmol) in 15 mL of THF is added dropwise and the resulting solution is stirred at −78° C. for 3 hours. The mixture is warmed to 0° C., quenched with saturated NaHCO3 solution and diluted with H2O and Et2O. The layers are separated. The organic phase is washed with saturated NaHCO3 solution, H2O and saturated NaCl solution, then dried over MgSO4, filtered and concentrated. The crude residue is purified via flash column chromatography eluting with a gradient of 10% EtOAc/hexanes to 30% EtOAc/hexanes to provide the title compound (3.64 g, 10.0 mmol). 1H NMR (CDCl3, 300 MHz) δ8.70 (s, 1H), 8.01 (dd, 1H), 7.80 (d, 2H), 7.70 (s, 1H), 7.60 (d, 1H), 7.38 (m, 2H), 4.00 (s, 3H), 2.49 (s, 3H).

Workup

  1. additionis added dropwise
  2. temperatureThe mixture is warmed to 0° C.
  3. customquenched with saturated NaHCO3 solution
  4. additiondiluted with H2O and Et2O
  5. customThe layers are separated
  6. washThe organic phase is washed with saturated NaHCO3 solution, H2O and saturated NaCl solution
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude residue is purified via flash column chromatography
  11. washeluting with a gradient of 10% EtOAc/hexanes to 30% EtOAc/hexanes

Sources & evidence

ORD record
ord-35882d2b05fe47fa8df931645fdb8ce0
Source dataset
uspto-grants-2009_11
Patent number
US07612075B2

Reaction notes

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