4-Fluoro-2-methylaniline → 1-(4-Fluoro-2-methylphenyl)piperazine dihydrochloride
Reaction equation
[ClH:1].[Cl:2][CH2:3][CH2:4][NH:5][CH2:6][CH2:7]Cl.[F:9][C:10]1[CH:16]=[CH:15][C:13]([NH2:14])=[C:12]([CH3:17])[CH:11]=1>CC(O)C>[ClH:2].[ClH:1].[F:9][C:10]1[CH:16]=[CH:15][C:13]([N:14]2[CH2:7][CH2:6][NH:5][CH2:4][CH2:3]2)=[C:12]([CH3:17])[CH:11]=1Participants
4
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 100 °C
Procedure
Bis(2-chloroethyl)amine hydrochloride (1.79 g, 10.03 mmol) and 4-fluoro-2-methylaniline (1.26 g, 10.07 mmol) were dissolved in 2-propanol (Volume: 10 mL) and stirred in a closed vial at 100° C. overnight. The reaction mixture was diluted with i-PrOH (10 mL) and cooled to 10° C. The resulting precipitate was filtered and purified using HPLC (10-80% ACN in water, TFA-buffered). The fractions were concentrated in vacuo, suspended in ether (3 mL) and treated with 4N HCl in dioxane (1 mL). The precipitate was filtered and dried in vacuum to afford 1-(4-fluoro-2-methylphenyl)piperazine dihydrochloride (150 mg, 0.561 mmol, 5.60% yield). ESI-MS: m/z 195 (M+H)+.
Workup
- temperaturecooled to 10° C
- filtrationThe resulting precipitate was filtered
- custompurified
- concentrationThe fractions were concentrated in vacuo
- additiontreated with 4N HCl in dioxane (1 mL)
- filtrationThe precipitate was filtered
- customdried in vacuum
Sources & evidence
- ORD record
- ord-52a4ac6ee2634f0a8cf02df52a8f2c8b
- Source dataset
- uspto-grants-2015_11
- Patent number
- US09187497B2
Reaction notes
Loading…