Acetic Acid → 4-[2-[4-(2-Pyridinyl)-1-piperazinyl]ethyl]cyclohexanone

HRID 893334Notes

Reaction equation

HRID 893334 reaction equation
O1[C:5]2([CH2:10][CH2:9][CH:8]([CH2:11][C:12]([N:14]3[CH2:19][CH2:18][N:17]([C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][N:21]=4)[CH2:16][CH2:15]3)=O)[CH2:7][CH2:6]2)[O:4]CC1.[BH4-].[Na+].B(F)(F)F.CCOCC.C(O)(=O)C>O1CCCC1>[N:21]1[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=1[N:17]1[CH2:18][CH2:19][N:14]([CH2:12][CH2:11][CH:8]2[CH2:9][CH2:10][C:5](=[O:4])[CH2:6][CH2:7]2)[CH2:15][CH2:16]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 8000Boron trifluoride etherateHCID 4311764Sodium borohydrideHCID 151011221-(1,4-Dioxaspiro[4,5]dec-8-ylacetyl)-4-(2-pyridinyl)piperazine

Product 1

HCID 151011114-[2-[4-(2-Pyridinyl)-1-piperazinyl]ethyl]cyclohexanoneYield 68.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

A solution of 1-(1,4-dioxaspiro[4,5]dec-8-ylacetyl)-4-(2-pyridinyl)piperazine (17.0 g) in 500 mL of dry tetrahydrofuran is treated with sodium borohydride (6.81 g) under nitrogen and the resulting suspension is treated dropwise with a solution of boron trifluoride etherate (29.5 mL) in 100 mL of tetrahydrofuran. The reaction mixture is stirred at room temperature overnight. A solution of glacial acetic acid (10.3 mL) in 100 mL of tetrahydrofuran is added dropwise, and the mixture stirred at room temperature for 2 hours. The solvent is evaporated in vacuo and the residue refluxed with 250 mL of a 10% solution of hydrochloric acid and 250 mL of acetone for 2 hours. The mixture is concentrated in vacuo to about one-half of the original volume. The remaining aqueous solution is washed twice with ethyl acetate and made basic with ammonium hydroxide. The crude product is extracted into ethyl acetate (2×300 mL). the organic extract is dried over magnesium sulfate and concentrated in vacuo. The reaction mixture is purified by MPLC (silica; 2% methanol, 98% chloroform) to give 9.73 g of the title compound as a colorless solid; mp 104°-106° C.

Workup

  1. stirringthe mixture stirred at room temperature for 2 hours
  2. customThe solvent is evaporated in vacuo
  3. temperaturethe residue refluxed with 250 mL of a 10% solution of hydrochloric acid and 250 mL of acetone for 2 hours
  4. concentrationThe mixture is concentrated in vacuo to about one-half of the original volume
  5. washThe remaining aqueous solution is washed twice with ethyl acetate
  6. extractionThe crude product is extracted into ethyl acetate (2×300 mL)
  7. extractionthe organic extract
  8. dry with materialis dried over magnesium sulfate
  9. concentrationconcentrated in vacuo
  10. customThe reaction mixture is purified by MPLC (silica; 2% methanol, 98% chloroform)

Sources & evidence

ORD record
ord-2523dc065dc449be9b97a4b666a2cba5
Source dataset
uspto-grants-1992_06
Patent number
US05124332

Reaction notes

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