Acetaldehyde → HCID 19970922, compound

HRID 975150Notes

Reaction equation

HRID 975150 reaction equation
C([Li])(C)(C)C.CCCCCC.Br[C:13]1[CH:14]=[C:15]2[C:19](=[CH:20][CH:21]=1)[NH:18][CH:17]=[C:16]2[CH:22]1[CH2:27][CH2:26][N:25]([CH3:28])[CH2:24][CH2:23]1.[CH:29](=[O:31])[CH3:30]>O1CCCC1>[OH:31][CH:29]([C:13]1[CH:14]=[C:15]2[C:19](=[CH:20][CH:21]=1)[NH:18][CH:17]=[C:16]2[CH:22]1[CH2:27][CH2:26][N:25]([CH3:28])[CH2:24][CH2:23]1)[CH3:30]

Participants

6

Reactant 4

HCID 177AcetaldehydeHCID 8058HexaneHCID 157453445-bromo-3-(1-methylpiperidin-4-yl)-1H-indoleHCID 178418306HCID 178418306, compound

Product 1

HCID 19970922HCID 19970922, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A 1.7M solution of t-butyllithium in hexane (8.03 ml, 13.65 mmol) was added dropwise, under nitrogen, to a stirred solution of 5-bromo-3-(N-methyl-4-piperidyl)-1H-indole (EP-A-0303507, 1.0 g, 3.4 mmol) in dry tetrahydrofuran (35 ml) at about -70° C., ensuring that the temperature of the reaction mixture did not rise above -50° C. during the addition. The resulting mixture was allowed to warm to room temperature over a period of 1 hour, then cooled to about -70° C. and treated, dropwise, with a solution of acetaldehyde (0.15 g, 3.4 mmol) in dry tetrahydrofuran (5 ml). After being stirred for a further 0.5 hour at about -70° C., the reaction mixture was quenched with water and allowed to warm to room temperature. The bulk of the organic solvents was removed by evaporation under reduced pressure and the remaining mixture partitioned between ethyl acetate and 10% aqueous ammonium chloride solution. The organic phase was separated, combined with two further ethyl acetate extracts of the aqueous phase, dried (Na2SO4) and evaporated under reduced pressure to give an oil which was purified by column chromatography on silica gel, eluting with 0.880 aqueous ammonia:methanol:dichloromethane (1:20:79), to provide the title compound which was employed in the following Example without further characterisation.

Workup

  1. additiondid not rise above -50° C. during the addition
  2. temperaturecooled to about -70° C.
  3. additiontreated
  4. customthe reaction mixture was quenched with water
  5. temperatureto warm to room temperature
  6. customThe bulk of the organic solvents was removed by evaporation under reduced pressure
  7. customthe remaining mixture partitioned between ethyl acetate and 10% aqueous ammonium chloride solution
  8. customThe organic phase was separated
  9. dry with materialdried (Na2SO4)
  10. customevaporated under reduced pressure
  11. customto give an oil which
  12. customwas purified by column chromatography on silica gel
  13. washeluting with 0.880 aqueous ammonia:methanol:dichloromethane (1:20:79)

Sources & evidence

ORD record
ord-424d961c705f47cc81ce23ba4c898d9b
Source dataset
uspto-grants-1997_03
Patent number
US05607960

Reaction notes

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