Tetrahydrofuran → 1-[2-(2-Oxazolyl)phenyl]-4-(phenylmethyl)piperazine
Reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1COCC1.C([Li])CCC.F[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[C:31]1[O:32][CH:33]=[CH:34][N:35]=1>O>[CH2:1]([N:8]1[CH2:13][CH2:12][N:11]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=2[C:31]2[O:32][CH:33]=[CH:34][N:35]=2)[CH2:10][CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1Participants
Conditions
- Temperature
- 0 °C
Procedure
A mixture of N-benzylpiperazine (3.56 g, 20.2 mmol) and THF (25 mL) was cooled to 0° C. and n-butyllithium (2.5M in hexanes, 7.6 mL, 19 mmol) was added. The mixture was cooled 30 minutes with stirring at 0° C., stirred 1 hour at 25° C., then cooled to 0° C. and 2-fluoro-1-oxazol-2-ylbenzene (1.1 g, 6.75 mmol) was added slowly. The reaction mixture was allowed to warm to 25° C., then stirred 90 minutes and diluted with water. The aqueous layer was separated and extracted with ethyl acetate (3×30 mL). The combined extracts were washed with brine, dried (MgSO4) and concentrated. The residue was purified on silica gel by column chromatography eluting with hexanes/ethyl acetate (9:1) to give 4-benzyl-1-(2-oxazol-2-ylphenyl)piperazine (0.805 g, 2.52 mmol).
Workup
- temperatureThe mixture was cooled 30 minutes
- stirringstirred 1 hour at 25° C.
- temperaturecooled to 0° C.
- temperatureto warm to 25° C.
- stirringstirred 90 minutes
- customThe aqueous layer was separated
- extractionextracted with ethyl acetate (3×30 mL)
- washThe combined extracts were washed with brine
- dry with materialdried (MgSO4)
- concentrationconcentrated
- customThe residue was purified on silica gel by column chromatography
- washeluting with hexanes/ethyl acetate (9:1)
Sources & evidence
- ORD record
- ord-bef7c156cbb044038036b4f035a8d203
- Source dataset
- uspto-grants-1999_01
- Patent number
- US05859014
Reaction notes
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