Potassium hydride → HCID 22611453, compound

HRID 725967Notes

Reaction equation

HRID 725967 reaction equation
[H-].[K+].Br[C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[NH:9][CH:8]=[C:7]2[CH:13]1[CH2:18][CH2:17][N:16]([CH3:19])[CH2:15][CH2:14]1.C([Li])(C)(C)C.CN(OC)[C:27](=[O:35])[C:28]1[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][CH:29]=1>O1CCCC1>[Cl:34][C:31]1[CH:32]=[CH:33][C:28]([C:27]([C:4]2[CH:5]=[C:6]3[C:10](=[CH:11][CH:12]=2)[NH:9][CH:8]=[C:7]3[CH:13]2[CH2:18][CH2:17][N:16]([CH3:19])[CH2:15][CH2:14]2)=[O:35])=[CH:29][CH:30]=1

Participants

6

Reactant 4

HCID 82127Potassium hydrideHCID 112756634-Chloro-N-methoxy-N-methylbenzamideHCID 157453445-bromo-3-(1-methylpiperidin-4-yl)-1H-indoleHCID 178418306HCID 178418306, compound

Product 1

HCID 22611453HCID 22611453, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-78 °C

Procedure

To a suspension of 0.21 gm (1.05 mMol) potassium hydride in 5.0 mL tetrahydrofuran at 0° C. were added a solution of 0.3 gm (1.0 mMol) 5-bromo-3-(1-methylpiperidin-4-yl)-1H-indole in 5.0 mL tetrahydrofuran and the solution stirred for about 30 minutes. The resulting mixture was cooled to about -78° C. and to it were added 1.47 mL (2.3 mMol) t-butyllithium, which had been precooled to -78° C., via cannula. After about 15 minutes, a solution of 1.0 gm (5.0 mMol) N-methyl-N-methoxy-4-chlorobenzamide (Preparation VII) in 3.0 mL tetrahydrofuran were added. The reaction mixture was allowed to gradually warm to ambient and was then quenched with 2N sodium hydroxide. The mixture extracted well with diethyl ether and the ether extracts were then washed with saturated aqueous sodium chloride, dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by radial chromatography (2 mm silica), eluting with 95:5 ethyl acetate:methanol, to give the title compound as a light yellow solid.

Workup

  1. customhad been precooled to -78° C., via cannula
  2. waitAfter about 15 minutes
  3. temperatureto gradually warm to ambient and
  4. customwas then quenched with 2N sodium hydroxide
  5. extractionThe mixture extracted well with diethyl ether
  6. washthe ether extracts were then washed with saturated aqueous sodium chloride
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by radial chromatography (2 mm silica)
  10. washeluting with 95:5 ethyl acetate

Sources & evidence

ORD record
ord-e131bfda64904198a40b67a3d2805d54
Source dataset
uspto-grants-1998_01
Patent number
US05708008

Reaction notes

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