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

HRID 1790452Notes

Reaction equation

HRID 1790452 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]([CH2:33][OH: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 220378911-[1-(4-Fluorophenethyl)piperidin-4-yl]-6-hydroxymethylindoline

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolventHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A 2.5 M solution (100 ml) of n-butyllithium in hexane was added dropwise at −78° C. into a solution (2 l) of 1-[1-(4-fluorophenethyl)piperidin-4-yl]-6-bromoindoline (80 g) in tetrahydrofuran over 15 min. After 10 min, dimethylformamide (23.2 ml) was added thereto and the resultant mixture was warmed to room temperature. Next, a saturated aqueous solution of ammonium chloride (400 ml) and ethyl acetate (1 l) 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 the resulting reside were added ethanol (240 ml) and sodium borohydride (7.6 g) and the resultant mixture was stirred at room temperature for 1 hr. After adding ice water (480 ml) to the reaction solution, the resulting crystals were collected by filtration, washed with water and air-dried at 50° C. over day and night to give the title compound (about 71 g) as a yellow powder. A portion of this crude product was purified by silica gel column chromatography (ethyl acetate/methanol system) followed by conversion into a hydrochloride in a conventional manner to give the hydrochloride of the title compound as a pale purple 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. additionTo the resulting reside were added ethanol (240 ml) and sodium borohydride (7.6 g)
  6. additionAfter adding ice water (480 ml) to the reaction solution
  7. filtrationthe resulting crystals were collected by filtration
  8. washwashed with water
  9. customair-dried at 50° C. over day and night

Sources & evidence

ORD record
ord-0e74d73763f4442bb6e38f8eb19be79d
Source dataset
uspto-grants-2006_07
Patent number
US07071201B2

Reaction notes

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