Hexane → 1-(1-Methyl-2-piperidyl)ethyl 1-methylindazole-3-carboxylate

HRID 5873

Reaction equation

HRID 5873 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][CH2:5][CH2:4][CH:3]1[CH:8]([OH:10])[CH3:9].[CH3:11]CCCCC.[Li]CCCC.C[C:23]1[CH:31]=[CH:30][CH:29]=[C:28]2[C:24]=1[C:25]([C:32](Cl)=[O:33])=[N:26][NH:27]2>C1COCC1.CN1CCN(C)C1=O>[CH3:11][N:27]1[C:28]2[C:24](=[CH:23][CH:31]=[CH:30][CH:29]=2)[C:25]([C:32]([O:10][CH:8]([CH:3]2[CH2:4][CH2:5][CH2:6][CH2:7][N:2]2[CH3:1])[CH3:9])=[O:33])=[N:26]1

Participants

7

Reactant 4

HCID 8058HexaneHCID 262597(1-Methyl-2-piperidyl)-1-ethanolHCID 534043614-Methyl-1H-indazole-3-carbonyl chlorideHCID 178418339Butyllithium

Product 1

HCID 197944571-(1-Methyl-2-piperidyl)ethyl 1-methylindazole-3-carboxylate

Reagents, catalysts & solvents 2

HCID 66611,3-Dimethyl-2-imidazolidinoneSolvent2×HCID 8028TetrahydrofuranSolvent2×

Procedure

(1-Methyl-2-piperidyl)-1-ethanol (4.5 g, 31 mmol) was dissolved in dry THF (70 ml) and 1,3-dimethyl-2-imidazolidinone (20 ml) was added. The solution was ice-cooled and a hexane solution of n-BuLi (1.6M, 20 ml) was added dropwise. The reaction solution was stirred at room temperature for 20 minutes, to which was added dropwise a solution of 1 methylindazole-3-carboxylic acid chloride (5.4 g, 28 mmol) dissolved in a mixed solution of dry THF (70 ml) and 1,3-dimethyl-2-imidazolidinone (20 ml). The mixture was stirred overnight at room temperature, the reaction solution was concentrated under reduced pressure and a 5% sodium bicarbonate solution was added. It was extracted with chloroform. The organic layer was washed with a saturated sodium chloride solution and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to obtain a residue. Separation and purification of the residue by silica gel column chromatography (110 g SiO2, chloroform:methanol=100:1) and further silica gel column chromatography with a different solvent (100 g SiO2, hexane:ethyl acetate=1:1) gave the title compound, 0.52 g of a high polar isomer and 0.64 g of a low polar isomer, respectively.

Workup

  1. temperaturecooled
  2. stirringThe mixture was stirred overnight at room temperature
  3. concentrationthe reaction solution was concentrated under reduced pressure
  4. additiona 5% sodium bicarbonate solution was added
  5. extractionIt was extracted with chloroform
  6. washThe organic layer was washed with a saturated sodium chloride solution
  7. dry with materialdried over anhydrous magnesium sulfate
  8. distillationThe solvent was distilled off under reduced pressure
  9. customto obtain a residue
  10. customSeparation and purification of the residue by silica gel column chromatography (110 g SiO2, chloroform:methanol=100:1) and further silica gel column chromatography with a different solvent (100 g SiO2, hexane:ethyl acetate=1:1)

Sources & evidence

ORD record
ord-6a23c604727f4daa90504cc1726ca6c2
Source dataset
uspto-grants-1993_09
Patent number
US05246945

Linked notes

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