1-Methylpiperazine → 1-(1-Benzhydrylazetidin-3-yl)-4-methylpiperazine

HRID 707509Notes

Reaction equation

HRID 707509 reaction equation
[C:1]1([CH:7]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[N:8]2[CH2:11][C:10](=O)[CH2:9]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:19][N:20]1[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)([O-])O.[Na+]>O.C(O)(=O)C.C1COCC1>[C:1]1([CH:7]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[N:8]2[CH2:11][CH:10]([N:23]3[CH2:24][CH2:25][N:20]([CH3:19])[CH2:21][CH2:22]3)[CH2:9]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

8

Reactant 4

HCID 531671-MethylpiperazineHCID 516892Sodium BicarbonateHCID 37355581-(Diphenylmethyl)azetidin-3-oneHCID 5049666Sodium triacetoxyborohydride

Product 1

HCID 222591561-(1-Benzhydrylazetidin-3-yl)-4-methylpiperazineYield 89.4%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a mixed solution of a commercially available product of 1-(diphenylmethyl)azetidin-3-one (1.00 g, 4.21 mmol), THF (20 mL) and acetic acid (1.00 mL) was added methylpiperazine (561 μL, 5.05 mmol) at room temperature. The resultant mixture was stirred at room temperature for 15 minutes. To the reaction mixture was added sodium triacetoxyborohydride (1.79 g, 8.42 mmol) at room temperature, and the resultant mixture was stirred at room temperature for 2 hours and 15 minutes. Sodium hydrogen carbonate and water were added to the reaction mixture, and the resultant mixture was extracted with ethyl acetate. An organic layer was washed with saturated brine, then dried over anhydrous magnesium sulfate, and then filtrated. The solvent was evaporated under a reduced pressure, and the resultant residue was purified by silica gel column chromatography (ethyl acetate-methanol) and then further purified by NH silica gel column chromatography (heptane:ethyl acetate=1:1) to give the title compound (1.21 g, yield: 89%).

Workup

  1. extractionthe resultant mixture was extracted with ethyl acetate
  2. washAn organic layer was washed with saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. filtrationfiltrated
  5. customThe solvent was evaporated under a reduced pressure
  6. customthe resultant residue was purified by silica gel column chromatography (ethyl acetate-methanol)
  7. customfurther purified by NH silica gel column chromatography (heptane:ethyl acetate=1:1)

Sources & evidence

ORD record
ord-fdea08d0274e477a83d868d3f09f6acc
Source dataset
uspto-grants-2015_11
Patent number
US09174998B2

Reaction notes

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