Dimethylformamide → 1-[1-(2-Fluorophenethyl)piperidin-4-yl]-6-formylindoline

HRID 1790505Notes

Reaction equation

HRID 1790505 reaction equation
[F:1][C:2]1[CH:25]=[CH:24][CH:23]=[CH:22][C:3]=1[CH2:4][CH2:5][N:6]1[CH2:11][CH2:10][CH:9]([N:12]2[C:20]3[C:15](=[CH:16][CH:17]=[C:18](Br)[CH:19]=3)[CH2:14][CH2:13]2)[CH2:8][CH2:7]1.CN(C)[CH:28]=[O:29].[Cl-].[NH4+].C(OCC)(=O)C>CCCCCC.O1CCCC1>[F:1][C:2]1[CH:25]=[CH:24][CH:23]=[CH:22][C:3]=1[CH2:4][CH2:5][N:6]1[CH2:11][CH2:10][CH:9]([N:12]2[C:20]3[C:15](=[CH:16][CH:17]=[C:18]([CH:28]=[O:29])[CH:19]=3)[CH2:14][CH2:13]2)[CH2:8][CH2:7]1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 8857Ethyl AcetateHCID 25517Ammonium ChlorideHCID 220380011-[1-(2-Fluorophenethyl)piperidin-4-yl]-6-bromoindoline

Product 1

HCID 220379081-[1-(2-Fluorophenethyl)piperidin-4-yl]-6-formylindolineYield 91.5%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent

Procedure

A 1.6 M solution (24 ml) of n-(butyllithium) in hexane was added dropwise at −78° C. over 10 min into a solution of 1-[1-(2-fluorophenethyl)piperidin-4-yl]-6-bromoindoline (12 g) obtained in Example 348-2) in tetrahydrofuran (200 ml). After 10 min, dimethylformamide (3.5 ml) was added thereto and the resultant mixture was allowed to warm to room temperature. Then a saturated aqueous solution (100 ml) of ammonium chloride and ethyl acetate (200 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. The resulting obtained was purified by silica gel column chromatography (ethyl acetate/ethanol system) to give the title compound (9.6 g) as a yellow powder (yield: 91.5%).

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. customThe resulting obtained
  6. customwas purified by silica gel column chromatography (ethyl acetate/ethanol system)

Sources & evidence

ORD record
ord-286c2e757c554ba2b8f51cc0a8f53262
Source dataset
uspto-grants-2006_07
Patent number
US07071201B2

Reaction notes

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