Trifluoroacetic acid → 2,6-Di-tert-butyl-4-[(piperazin-1-yl)methyl]phenol

HRID 1977128Notes

Reaction equation

HRID 1977128 reaction equation
CC(C)(O[C:5]([N:7]1[CH2:12][CH2:11][NH:10][CH2:9][CH2:8]1)=O)C.[CH3:14][C:15]([C:18]1[CH:19]=[C:20]([CH:23]=[C:24]([C:27]([CH3:30])([CH3:29])[CH3:28])[C:25]=1[OH:26])C=O)([CH3:17])[CH3:16].C([BH3-])#N.[Na+].C([O-])(O)=O.[Na+].FC(F)(F)C(O)=O>CO.C1COCC1>[CH3:17][C:15]([C:18]1[CH:19]=[C:20]([CH2:5][N:7]2[CH2:8][CH2:9][NH:10][CH2:11][CH2:12]2)[CH:23]=[C:24]([C:27]([CH3:30])([CH3:29])[CH3:28])[C:25]=1[OH:26])([CH3:14])[CH3:16]

Participants

8

Reactant 5

HCID 6422Trifluoroacetic acidHCID 732193,5-Di-tert-butyl-4-hydroxybenzaldehydeHCID 143452tert-Butyl piperazine-1-carboxylateHCID 516892Sodium BicarbonateHCID 5003444Sodium cyanoborohydride

Product 1

HCID 128958282,6-Di-tert-butyl-4-[(piperazin-1-yl)methyl]phenol

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

Commercially available (1,1-dimethylethoxy)carbonylpiperazine (12.47 g) and 3,5-bis(1,1-dimethylethyl)-4-hydroxybenzaldehyde (15.67 g) were dissolved in 1:1 mixture of methanol and THF (200 ml). The solution was cooled in an ice-bath, and sodium cyanoborohydride (6.2 g) was added portionwise over 2 h. The reaction mixture was allowed to warm to room temperature and stirred for 48 h. At this time 50 ml of a saturated solution of NaHCO3 was added, and the mixture was concentrated in vacuo. The residue was diluted with water and extracted with dichloromethane. The organic fractions (3×500 ml) were washed with water, brine and dried over sodium sulphate. After removal of the solvent in vacuo, the viscous material was dissolved in trifluoroacetic acid (100 ml) and stirred at room temperature overnight. The reaction mixture was concentrated in vacuo and the residue was triturated with diethyl ether to afford a white solid. A small amount of this trifluoroacetic acid salt was converted into the corresponding free base and analysed as the required product. The product can be isolated as its free base by simple modification of the above described procedure.

Workup

  1. temperatureThe solution was cooled in an ice-bath
  2. concentrationthe mixture was concentrated in vacuo
  3. additionThe residue was diluted with water
  4. extractionextracted with dichloromethane
  5. washThe organic fractions (3×500 ml) were washed with water, brine
  6. dry with materialdried over sodium sulphate
  7. customAfter removal of the solvent in vacuo
  8. dissolutionthe viscous material was dissolved in trifluoroacetic acid (100 ml)
  9. stirringstirred at room temperature overnight
  10. concentrationThe reaction mixture was concentrated in vacuo
  11. customthe residue was triturated with diethyl ether
  12. customto afford a white solid

Sources & evidence

ORD record
ord-20631361f5464990a6fb72a9dd47b95a
Source dataset
uspto-grants-2001_05
Patent number
US06232314B1

Reaction notes

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