Hexamethylphosphoramide → 2-(4-hydroxytetrahydro-4H-4-pyranyl)-5-methylthio-1-benzenesulfonylindole

HRID 1814081Notes

Reaction equation

HRID 1814081 reaction equation
[CH3:1][S:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[N:8]([S:12]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)(=[O:14])=[O:13])[CH:7]=[CH:6]2.CN(C)P(=O)(N(C)C)N(C)C.[O:32]1[CH2:37][CH2:36][C:35](=[O:38])[CH2:34][CH2:33]1.[Cl-].[NH4+]>O1CCCC1.C([Li])CCC>[OH:38][C:35]1([C:7]2[N:8]([S:12]([C:15]3[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=3)(=[O:13])=[O:14])[C:9]3[C:5]([CH:6]=2)=[CH:4][C:3]([S:2][CH3:1])=[CH:11][CH:10]=3)[CH2:36][CH2:37][O:32][CH2:33][CH2:34]1

Participants

7

Reactant 4

HCID 12679HexamethylphosphoramideHCID 25517Ammonium ChlorideHCID 121599Tetrahydro-4H-pyran-4-oneHCID 225044271-Benzenesulfonyl-5-methylthioindole

Product 1

HCID 225044372-(4-hydroxytetrahydro-4H-4-pyranyl)-5-methylthio-1-benzenesulfonylindole

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 178418339ButyllithiumSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of 5-methylthio-1-benzenesulfonylindole (200 mg) in tetrahydrofuran (5 ml), n-butyl lithium (0.49 ml, 1.61 M) was added at −78° C. under nitrogen atmosphere and the mixture was stirred at −78° C. for 30 minutes, followed by addition of hexamethylphosphoric triamide (0.23 ml), and the mixture was stirred for 15 minutes. Subsequently, tetrahydro-4H-pyran-4-one (0.12 ml) was added thereto and the mixture was stirred at −78° C. for 15 minutes and heated to 15 to 30° C. The reaction solution was then poured into a saturated aqueous ammonium chloride solution, extracted with dichloromethane, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The resulting residue was separated using silica gel preparative thin-layer chromatography (hexane:ethyl acetate=1:1) and (methanol:chloroform=1:20) to obtain 39 mg of the desired product as a colorless oil.

Workup

  1. stirringthe mixture was stirred for 15 minutes
  2. stirringthe mixture was stirred at −78° C. for 15 minutes
  3. temperatureheated to 15 to 30° C
  4. extractionextracted with dichloromethane
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe resulting residue was separated

Sources & evidence

ORD record
ord-2e783a9a069d40e299e0819c292a4277
Source dataset
uspto-grants-2005_04
Patent number
US06875770B2

Reaction notes

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