Ammonium Chloride → 1-[1-(4-Fluorophenethyl)piperidin-4-yl]-6-acetylindoline

HRID 1790445Notes

Reaction equation

HRID 1790445 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.[CH3:31][C:32](N(C)C)=[O:33].[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]([C:32](=[O:33])[CH3:31])[CH:26]=4)[CH2:21][CH2:20]3)[CH2:15][CH2:14]2)=[CH:9][CH:8]=1

Participants

8

Reactant 4

HCID 25517Ammonium ChlorideHCID 31374DimethylacetamideHCID 220378891-[1-(4-Fluorophenethyl)piperidin-4-yl]-6-bromoindolineHCID 178418339Butyllithium

Product 1

HCID 220381171-[1-(4-Fluorophenethyl)piperidin-4-yl]-6-acetylindolineYield 27%

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolventHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A 2.5 M solution (1.5 ml) of n-butyllithium in hexane was added dropwise at −78° C. into a solution (30 ml) of 1-[1-(4-fluorophenethyl)piperidin-4-yl]-6-bromoindoline (1.0 g) in tetrahydrofuran over 5 min. After 10 min, dimethylacetamide (0.34 ml) was added thereto and the resultant mixture was warmed to room temperature. Next, a saturated aqueous solution of ammonium chloride and ethyl acetate were added thereto to and the layers were separated. The organic layer was washed with brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by NH-silica gel column chromatography (hexane/ethyl acetate system) to give the title compound (250 mg) as a yellow powder (yield: 27%).

Workup

  1. customto and the 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. customThe residue was purified by NH-silica gel column chromatography (hexane/ethyl acetate system)

Sources & evidence

ORD record
ord-e3eec821340f44e9a277867fc7a6326b
Source dataset
uspto-grants-2006_07
Patent number
US07071201B2

Reaction notes

Loading…