Methanol → HCID 178468979, compound

HRID 1977309Notes

Reaction equation

HRID 1977309 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][CH:19]1[CH2:24][CH2:23][C:22](=O)[CH2:21][CH2:20]1.CO.C([BH3-])#N.[Na+]>C(O)(=O)C>[CH3:18][C@@H:19]1[CH2:24][CH2:23][C@H:22]([N:4]2[CH2:3][CH2:2][N:1]([C:7]3[CH:8]=[CH:9][C:10]([C:11]([O:13][CH2:14][CH3:15])=[O:12])=[CH:16][CH:17]=3)[CH2:6][CH2:5]2)[CH2:21][CH2:20]1.[CH3:18][C@H:19]1[CH2:24][CH2:23][C@H:22]([N:4]2[CH2:3][CH2:2][N:1]([C:7]3[CH:8]=[CH:9][C:10]([C:11]([O:13][CH2:14][CH3:15])=[O:12])=[CH:16][CH:17]=3)[CH2:6][CH2:5]2)[CH2:21][CH2:20]1

Participants

7

Reactant 4

HCID 887MethanolHCID 115254-MethylcyclohexanoneHCID 2761178Ethyl 4-(piperazin-1-yl)benzoateHCID 5003444Sodium cyanoborohydride

Product 2

HCID 178468979HCID 178468979, compoundHCID 178468980HCID 178468980, compound

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

To an ice-cooled solution of ethyl 4-(piperazin-1-yl)benzoate (2.00 g) and 4-methylcyclohexanone (1.05 ml) in a mixed solvent of methanol (40 ml) and acetic acid (1.47 ml) was added sodium cyanoborohydride (0.59 g) in a stream of nitrogen. The mixture was stirred at this temperature for 1 hour and at room temperature for 17 hours. The reaction mixture was quenched with saturated aqueous sodium hydrogen carbonate solution and the resulting precipitate was collected by filtration, washed thoroughly with water and dried to give a mixture of cis and trans products. This mixture was separated by column chromatography on silica gel eluting with a mixed solvent of methylene chloride-methanol (from 0% to 2% gradient solution) to give ethyl 4-[4-(cis-4-methylcyclohexyl)piperazin-1-yl]benzoate (0.80 g) as a pale green solid and ethyl 4-[4-(trans-4-methylcyclohexyl)piperazin-1-yl]benzoate (0.64 g) as a pale green solid. Trans-product was confirmed by X-ray crystal analysis.

Workup

  1. customThe reaction mixture was quenched with saturated aqueous sodium hydrogen carbonate solution
  2. filtrationthe resulting precipitate was collected by filtration
  3. washwashed thoroughly with water
  4. customdried
  5. customto give
  6. additiona mixture of cis and trans products
  7. customThis mixture was separated by column chromatography on silica gel eluting with a mixed solvent of methylene chloride-methanol (from 0% to 2% gradient solution)

Sources & evidence

ORD record
ord-50db6826c6b8457696017bbaac80f2c3
Source dataset
uspto-grants-2001_05
Patent number
US06232290B1

Reaction notes

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