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

HRID 704590Notes

Reaction equation

HRID 704590 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-yl-acetyl)-4-(2-pyridinyl)piperazine (17.0 g) (Example I) 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 two 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 two 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 two 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 two 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-005e0547dd0e47e588a78a9b71024b57
Source dataset
uspto-grants-1991_01
Patent number
US04988699

Reaction notes

Loading…