Methanol → 4-[4-(1-Methoxy-1,1'-bicyclohexan-4-yl)piperazinyl]benzoic acid ethyl ester

HRID 1816765Notes

Reaction equation

HRID 1816765 reaction equation
[N:1]1([C:7]2[CH:17]=[CH:16][C:10]([C:11]([O:13][CH2:14][CH3:15])=[O:12])=[CH:9][CH:8]=2)[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.[CH3:18][O:19][C:20]1([CH:27]2[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]2)[CH2:25][CH2:24][C:23](=O)[CH2:22][CH2:21]1.CO.C([BH3-])#N.[Na+]>C(O)(=O)C.O1CCCC1>[CH2:14]([O:13][C:11](=[O:12])[C:10]1[CH:9]=[CH:8][C:7]([N:1]2[CH2:2][CH2:3][N:4]([CH:23]3[CH2:24][CH2:25][C:20]([O:19][CH3:18])([CH:27]4[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]4)[CH2:21][CH2:22]3)[CH2:5][CH2:6]2)=[CH:17][CH:16]=1)[CH3:15]

Participants

7

Reactant 4

HCID 887MethanolHCID 2761178Ethyl 4-(piperazin-1-yl)benzoateHCID 5003444Sodium cyanoborohydrideHCID 224929241-Methoxy-1,1'-bicyclohexane-4-one

Product 1

HCID 541335744-[4-(1-Methoxy-1,1'-bicyclohexan-4-yl)piperazinyl]benzoic acid ethyl esterYield 42.9%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 8028TetrahydrofuranSolvent

Procedure

To an ice cooled solution of ethyl 4-(piperazin-1-yl)benzoate (1.23 g) and 1-methoxy-1,1′-bicyclohexane-4-one (916 mg) in a mixed solvent of methanol (20 ml), tetrahydrofuran (15 ml) and acetic acid (0.74 ml) was added sodium cyanoborohydride (301 mg) in a stream of nitrogen. The mixture was stirred at this temperature for 1.5 hours and at room temperature for 7.5 hours. The reaction mixture was quenched with saturated aqueous sodium hydrogen carbonate solution. Dichloromethane was added to the solution. The organic layer was taken, washed with sodium hydrogen carbonate solution and dried over magnesium sulfate. The magnesium sulfate was filtered off, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel chromatography (3:1 hexane-methanol elution) to give 4-[4-(1-methoxy-1,1′-bicyclohexan-4-yl)piperazinyl]benzoic acid ethyl ester (801 mg).

Workup

  1. customThe reaction mixture was quenched with saturated aqueous sodium hydrogen carbonate solution
  2. additionDichloromethane was added to the solution
  3. washwashed with sodium hydrogen carbonate solution
  4. dry with materialdried over magnesium sulfate
  5. filtrationThe magnesium sulfate was filtered off
  6. concentrationthe filtrate was concentrated under reduced pressure
  7. customThe residue was purified by silica gel chromatography (3:1 hexane-methanol elution)

Sources & evidence

ORD record
ord-e4a255101002494a8d0ec17fb2671aca
Source dataset
uspto-grants-2005_04
Patent number
US06884868B1

Reaction notes

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