Dimethylformamide → 1-[1-(4-Fluorophenethyl)piperidin-4-yl]-6-formylindoline

HRID 1790446Notes

Reaction equation

HRID 1790446 reaction equation
C([Li])CCC.[F:6][C:7]1[CH:30]=[CH:29][C:10]([CH2:11][CH2:12][N:13]2[CH2:18][CH2:17][CH:16]([N:19]3[C:27]4[C:22](=[CH:23][CH:24]=[C:25](Br)[CH:26]=4)[CH2:21][CH2:20]3)[CH2:15][CH2:14]2)=[CH:9][CH:8]=1.CN(C)[CH:33]=[O:34].[Cl-].[NH4+]>CCCCCC.O1CCCC1.C(OCC)(=O)C>[F:6][C:7]1[CH:30]=[CH:29][C:10]([CH2:11][CH2:12][N:13]2[CH2:18][CH2:17][CH:16]([N:19]3[C:27]4[C:22](=[CH:23][CH:24]=[C:25]([CH:33]=[O:34])[CH:26]=4)[CH2:21][CH2:20]3)[CH2:15][CH2:14]2)=[CH:9][CH:8]=1

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 25517Ammonium ChlorideHCID 220378891-[1-(4-Fluorophenethyl)piperidin-4-yl]-6-bromoindolineHCID 178418339Butyllithium

Product 1

HCID 220380721-[1-(4-Fluorophenethyl)piperidin-4-yl]-6-formylindoline

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolventHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A 2.5 M solution (50 ml) of n-butyllithium in hexane was added dropwise at −78° C. into a solution of 1-[1-(4-fluorophenethyl)piperidin-4-yl]-6-bromoindoline (40 g) in tetrahydrofuran (1 l) over 10 min. After 10 min, dimethylformamide (11.6 ml) was added thereto and the resultant mixture was warmed to room temperature. Next, a saturated aqueous solution of ammonium chloride (200 ml) and ethyl acetate (500 ml) were added thereto and the layers were separated. The organic layer was washed with brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give the crude title compound (37.5 g). A portion of this crude product was purified by silica gel column chromatography (ethyl acetate/ethanol system) to give the title compound as a yellow powder.

Workup

  1. customthe layers were separated
  2. washThe organic layer was washed with brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customto give the crude title compound (37.5 g)
  6. customA portion of this crude product was purified by silica gel column chromatography (ethyl acetate/ethanol system)

Sources & evidence

ORD record
ord-c538c94a90844577a538f940baee3bfb
Source dataset
uspto-grants-2006_07
Patent number
US07071201B2

Reaction notes

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