Diisopropylamine → 2-(1-Benzylpiperidin-4-yl)-1-(3-chloro-2-thienyl)ethanol

HRID 890019Notes

Reaction equation

HRID 890019 reaction equation
C(NC(C)C)(C)C.[Cl:8][C:9]1[CH:13]=[CH:12][S:11][CH:10]=1.[CH2:14]([N:21]1[CH2:26][CH2:25][CH:24]([CH2:27][CH:28]=[O:29])[CH2:23][CH2:22]1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.[Cl-].[NH4+]>O1CCCC1.C([Li])CCC.C(OCC)(=O)C>[CH2:14]([N:21]1[CH2:26][CH2:25][CH:24]([CH2:27][CH:28]([C:10]2[S:11][CH:12]=[CH:13][C:9]=2[Cl:8])[OH:29])[CH2:23][CH2:22]1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1

Participants

8

Reactant 4

HCID 7912DiisopropylamineHCID 25517Ammonium ChlorideHCID 870173-ChlorothiopheneHCID 100136024-Piperidineacetaldehyde, 1-(phenylmethyl)-

Product 1

HCID 222481782-(1-Benzylpiperidin-4-yl)-1-(3-chloro-2-thienyl)ethanolYield 59%

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolventHCID 178418339ButyllithiumSolvent

Procedure

After dissolving 1.3 ml of diisopropylamine in 20 ml of tetrahydrofuran, 3.5 ml of n-butyllithium (2.66 M, n-hexane solution) was added dropwise while stirring at below −30° C. After stirring for 30 minutes while cooling on ice, 0.86 ml of 3-chlorothiophene was added dropwise. The mixture was stirred for another 30 minutes, and then a solution of 1.68 g of 1-benzyl-4-piperidineacetaldehyde in tetrahydrofuran (5 ml) was added and stirring was continued for 1 hour. Saturated aqueous ammonium chloride solution was added to the reaction solution and extraction was performed with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (solvent: n-hexane/ethyl acetate) to obtain the title compound (1.53 g, 59% yield).

Workup

  1. additionwas added dropwise
  2. stirringAfter stirring for 30 minutes
  3. additionwas added dropwise
  4. stirringThe mixture was stirred for another 30 minutes
  5. stirringstirring
  6. washThe organic layer was washed with saturated brine
  7. dry with materialdried over anhydrous magnesium sulfate
  8. distillationthe solvent was distilled off under reduced pressure
  9. customThe residue was purified by silica gel column chromatography (solvent: n-hexane/ethyl acetate)

Sources & evidence

ORD record
ord-637e119ec0454fe9b5e785f83e462072
Source dataset
uspto-grants-2006_02
Patent number
US06995144B2

Reaction notes

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