Sodium Hydroxide → 1-[1-(3,4-Difluorophenethyl)-piperidin-4-yl]indoline

HRID 1790399Notes

Reaction equation

HRID 1790399 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH2:9][C:10](O)=O)[CH:5]=[CH:6][C:7]=1[F:8].[NH:13]1[CH2:18][CH2:17][CH:16]([N:19]2[C:27]3[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=3)[CH2:21][CH2:20]2)[CH2:15][CH2:14]1.[H-].[Al+3].[Li+].[H-].[H-].[H-].[OH-].[Na+]>O1CCCC1.C(OCC)(=O)C.O>[F:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][C:7]=1[F:8])[CH2:9][CH2:10][N:13]1[CH2:18][CH2:17][CH:16]([N:19]2[C:27]3[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=3)[CH2:21][CH2:20]2)[CH2:15][CH2:14]1

Participants

8

Reactant 4

HCID 14798Sodium HydroxideHCID 69571(3,4-Difluorophenyl)acetic acidHCID 21226445Aluminium lithium hydrideHCID 220286031-Piperidin-4-yl-2,3-dihydro-1H-indole

Product 1

HCID 220379761-[1-(3,4-Difluorophenethyl)-piperidin-4-yl]indolineYield 112.2%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

3,4-Difluorophenylacetic acid (0.095 g) was dissolved in tetrahydrofuran (5.0 ml). After adding 1,1-carbonyldiimidazole (0.089 g) to the resultant solution, the resultant mixture was stirred at room temperature for 15 min followedbytheadditionof 1-(piperidin-4-yl)indoline (0.1 g). After stirring at room temperature overnight, the resultant mixture was diluted with ethyl acetate, washed with brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate system) to give a colorless oil. Then this product was dissolved in tetrahydrofuran (2.5 ml) and lithium aluminum hydride (0.046 g) was added thereto under ice cooling followed by heating under reflux for 2 hr. After cooling the reaction solution, water (0.05 ml), a 5 N aqueous solution (0.05 ml) of sodium hydroxide and further water (0.15 ml) were added thereto. The precipitated solid was filtered off and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate system) to give the title compound (0.190 g) as a colorless oil (yield: quantitative).

Workup

  1. washwashed with brine
  2. dry with materialdried over anhydrous sodium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate system)
  5. customto give a colorless oil
  6. temperatureby heating
  7. temperatureunder reflux for 2 hr
  8. filtrationThe precipitated solid was filtered off
  9. concentrationthe filtrate was concentrated under reduced pressure
  10. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate system)

Sources & evidence

ORD record
ord-208f2bf09efd4eea8e8df35499530e4a
Source dataset
uspto-grants-2006_07
Patent number
US07071201B2

Reaction notes

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