Hydrochloric Acid → 1-Methyl-2-phenylpiperazine dihydrochloride

HRID 530624Notes

Reaction equation

HRID 530624 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][N:11]([CH3:14])[CH:10]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH2:9]1)=O)(C)(C)C.[ClH:21]>C1COCC1.O1CCOCC1>[ClH:21].[ClH:21].[CH3:14][N:11]1[CH2:12][CH2:13][NH:8][CH2:9][CH:10]1[C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 771800394-Boc-1-methyl-2-phenylpiperazine

Product 1

HCID 450750971-Methyl-2-phenylpiperazine dihydrochloride

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 312751,4-DioxaneSolvent

Procedure

To a mixture of tert-butyl 3-phenylpiperazine-1-carboxylate (288 mg, 1.1 mmol), and formaldehyde (185 mg, 6.16 mmol) in methanol (7 mL) was added sodium triacetoxyborohydride (949 mg, 4.48 mmol) at 0° C. After stirring for 3 h at room temperature, the reaction mixture was diluted with 10% sodium bicarbonate solution and ethyl acetate. The aqueous part was extracted with ethyl acetate and the combined organic part was dried over sodium sulfate, filtered, concentrated in vacuo. The residue was purified by flash chromatography (20/1 dichloromethane/methanol) to provide 4-methyl-3-phenyl-piperazine-1-carboxylic acid tert-butyl ester (307 mg, 101%). (M+H)+=277 m/e. To a solution of 4-methyl-3-phenyl-piperazine-1-carboxylic acid tert-butyl ester (307 mg, 1.11 mmol) in THF (3 mL) at 0° C. was added 4M HCl in dioxane (0.9 mL). The reaction mixture was stirred overnight and concentrated in vacuo. The residue was triturated with dichloromethane and filtered to provide 1-methyl-2-phenyl-piperazine dihydrochloride (290 mg), which was used as is for the next step.

Workup

  1. concentrationconcentrated in vacuo
  2. customThe residue was triturated with dichloromethane
  3. filtrationfiltered

Sources & evidence

ORD record
ord-f32996e8309d4e51b83890997496f980
Source dataset
uspto-grants-2016_05
Patent number
US09353096B2

Reaction notes

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