Sodium Carbonate → 1-[1-[1-(3-Methoxy-2-pyrazinyl)ethyl]piperidin-4-yl]-2-(2-fluorophenyl)ethanone

HRID 606249Notes

Reaction equation

HRID 606249 reaction equation
Cl.[F:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[CH2:9][C:10]([CH:12]1[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]1)=[O:11].[C:18]([C:21]1[C:26]([O:27][CH3:28])=[N:25][CH:24]=[CH:23][N:22]=1)(=O)[CH3:19].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)([O-])[O-].[Na+].[Na+]>C(O)C.CC(C)[O-].CC(C)[O-].CC(C)[O-].CC(C)[O-].[Ti+4].C(OCC)(=O)C.C(N(CC)CC)C>[CH3:28][O:27][C:26]1[C:21]([CH:18]([N:15]2[CH2:14][CH2:13][CH:12]([C:10](=[O:11])[CH2:9][C:4]3[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=3[F:2])[CH2:17][CH2:16]2)[CH3:19])=[N:22][CH:23]=[CH:24][N:25]=1

Participants

9

Reactant 4

HCID 10340Sodium CarbonateHCID 5398321-(3-Methoxy-2-pyrazinyl)ethanoneHCID 5049666Sodium triacetoxyborohydrideHCID 222481242-(2-Fluorophenyl)-1-(piperidin-4-yl)ethanone hydrochloride

Product 1

HCID 222484241-[1-[1-(3-Methoxy-2-pyrazinyl)ethyl]piperidin-4-yl]-2-(2-fluorophenyl)ethanoneYield 9.5%

Reagents, catalysts & solvents 4

HCID 11026Titanium isopropoxideCatalystHCID 702EthanolSolvent2×HCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Procedure

After dissolving 1.012 g of triethylamine in 10 ml of ethanol, 2.575 g of 2-(2-fluorophenyl)-1-(piperidin-4-yl)ethanone hydrochloride, 10 ml of ethanol, 2.951 ml of titanium (IV) tetraisopropoxide and 760 mg of 2-acetyl-3-methoxypyrazine were added in that order and the mixture was stirred for 5 hours and 20 minutes at room temperature. Next, 1.59 g of sodium triacetoxyborohydride was added to the reaction mixture and the mixture was stirred overnight at room temperature. A sodium carbonate solution and ethyl acetate were added to the reaction mixture and the mixture was filtered with celite. The filtrate was extracted with ethyl acetate, and the extract was washed with water and saturated brine and then dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and then the residue was dissolved in ethyl acetate and filtered with silica gel. The solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography (solvent: n-hexane/ethyl acetate) to obtain the title compound (169 mg, 9% yield).

Workup

  1. additionwere added in that order
  2. stirringthe mixture was stirred overnight at room temperature
  3. filtrationthe mixture was filtered with celite
  4. extractionThe filtrate was extracted with ethyl acetate
  5. washthe extract was washed with water and saturated brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. distillationThe solvent was distilled off under reduced pressure
  8. dissolutionthe residue was dissolved in ethyl acetate
  9. filtrationfiltered with silica gel
  10. distillationThe solvent was distilled off under reduced pressure
  11. customthe residue was purified by silica gel column chromatography (solvent: n-hexane/ethyl acetate)

Sources & evidence

ORD record
ord-96b71c48c6334d8183e248a605d6e34a
Source dataset
uspto-grants-2011_03
Patent number
US07915274B2

Reaction notes

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