p-(Trifluoromethoxy)benzaldehyde → 4-[4-(4-Trifluoromethoxybenzyl)piperazin-1-yl]phenol

HRID 856096Notes

Reaction equation

HRID 856096 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[F:14][C:15]([F:26])([F:25])[O:16][C:17]1[CH:24]=[CH:23][C:20]([CH:21]=O)=[CH:19][CH:18]=1.C([BH3-])#N.[Na+].C(=O)([O-])O.[Na+]>CO.C(Cl)Cl.C(O)(=O)C>[F:14][C:15]([F:25])([F:26])[O:16][C:17]1[CH:24]=[CH:23][C:20]([CH2:21][N:11]2[CH2:12][CH2:13][N:8]([C:5]3[CH:4]=[CH:3][C:2]([OH:1])=[CH:7][CH:6]=3)[CH2:9][CH2:10]2)=[CH:19][CH:18]=1

Participants

8

Reactant 4

HCID 69573p-(Trifluoromethoxy)benzaldehydeHCID 92467p-(1-Piperazinyl)phenolHCID 516892Sodium BicarbonateHCID 5003444Sodium cyanoborohydride

Product 1

HCID 307469694-[4-(4-Trifluoromethoxybenzyl)piperazin-1-yl]phenolYield 57%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 887MethanolSolventHCID 6344DichloromethaneSolvent2×

Procedure

4-(4-hydroxyphenyl)piperazine (3 g, 16.8 mmol) and 4-trifluoromethoxy benzaldehyde (3.36 g, 17.7 mmol) were dissolved in methanol (60 ml) and methylene chloride (15 ml). Sodium cyanoborohydride (1.59 g, 25.3 mmol) and-acetic acid (1.6 ml) were added to this solution while cooling in an ice-bath, and the mixture was stirred for 2 hours. Saturated sodium hydrogencarbonate aqueous solution and methylene chloride were added to the reaction mixture, which was extracted with methylene chloride. The extract was washed with brine, dried over magnesium sulfate, and then filtered. The filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (methylene chloride/methanol=100/1) to afford 4-[4-(4-trifluoromethoxybenzyl)piperazin-1-yl]phenol (3.36 g, yield 57%) as a colorless crystalline powder.

Workup

  1. temperaturewhile cooling in an ice-bath
  2. extractionwas extracted with methylene chloride
  3. washThe extract was washed with brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (methylene chloride/methanol=100/1)

Sources & evidence

ORD record
ord-639556ef32674948b8fae09e68ed14b9
Source dataset
uspto-grants-2007_08
Patent number
US07262212B2

Reaction notes

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