Acetic Acid → HCID 68525181, compound

HRID 1932545Notes

Reaction equation

HRID 1932545 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][N:11]([C:14]([C:16]2[CH:21]=[CH:20][C:19]([O:22][C:23]3[CH:28]=[CH:27][C:26]([NH:29][CH2:30][C:31]4[CH:36]=[CH:35][C:34]([C:37]([F:40])([F:39])[F:38])=[CH:33][CH:32]=4)=[CH:25][N:24]=3)=[CH:18][CH:17]=2)=[O:15])[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C=O.[C:43]([BH3-])#N.[Na+].C(O)(=O)C>CO>[CH2:1]([N:8]1[CH2:13][CH2:12][N:11]([C:14]([C:16]2[CH:17]=[CH:18][C:19]([O:22][C:23]3[CH:28]=[CH:27][C:26]([N:29]([CH3:43])[CH2:30][C:31]4[CH:32]=[CH:33][C:34]([C:37]([F:39])([F:40])[F:38])=[CH:35][CH:36]=4)=[CH:25][N:24]=3)=[CH:20][CH:21]=2)=[O:15])[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 68527120HCID 68527120, compound

Product 1

HCID 68525181HCID 68525181, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of (4-benzylpiperazin-1-yl){4-[5-(4-trifluoromethylbenzylamino)pyridin-2-yloxy]phenyl}methanone (5.40 g, 9.88 mmol) in methanol (150 mL) were added 37% aqueous formaldehyde (2.8 mL), sodium cyanoborohydride (1.86 g, 29.6 mmol) and acetic acid (1.7 mL) under ice cooling, and the resulting solution was stirred at room temperature for 2 hours. The solvent was evaporated under reduced pressure. Water was added to the residue, and this solution was neutralized with a saturated sodium bicarbonate solution, and extracted with chloroform. The organic layer was washed with water, and then dried over anhydrous magnesium sulfate. The solvent was evaporated, and the residue was purified by silica gel column chromatography (chloroform:methanol=60:1). To the resulting product was then added a solution of 4 M hydrogen chloride in ethyl acetate until the resulting solution had a pH of 1. The precipitates were collected by filtration and recrystallized from ethanol (80 mL), to thereby yield 2.5 g of the title compound.

Workup

  1. customThe solvent was evaporated under reduced pressure
  2. additionWater was added to the residue
  3. extractionextracted with chloroform
  4. washThe organic layer was washed with water
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customThe solvent was evaporated
  7. customthe residue was purified by silica gel column chromatography (chloroform:methanol=60:1)
  8. additionTo the resulting product was then added a solution of 4 M hydrogen chloride in ethyl acetate until the resulting solution
  9. filtrationThe precipitates were collected by filtration
  10. customrecrystallized from ethanol (80 mL)

Sources & evidence

ORD record
ord-7195ccdd32004422bbf9675df2150fee
Source dataset
uspto-grants-2012_05
Patent number
US08188277B2

Reaction notes

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