Carbon Dioxide → 3-[4-(4-Acetyl-2-fluoro-phenyl)-piperazine-1-carbonyl]-4-bromo benzonitrile

HRID 2374250Notes

Reaction equation

[Br:1][C:2]1[CH:10]=[CH:9][C:8]([C:11]#[N:12])=[CH:7][C:3]=1[C:4]([OH:6])=O.C(N1C=CN=C1)(N1C=CN=C1)=O.C(=O)=O.[F:28][C:29]1[CH:30]=[C:31]([C:41](=[O:43])[CH3:42])[CH:32]=[CH:33][C:34]=1[N:35]1[CH2:40][CH2:39][NH:38][CH2:37][CH2:36]1>CN(C=O)C>[C:41]([C:31]1[CH:32]=[CH:33][C:34]([N:35]2[CH2:36][CH2:37][N:38]([C:4]([C:3]3[CH:7]=[C:8]([CH:9]=[CH:10][C:2]=3[Br:1])[C:11]#[N:12])=[O:6])[CH2:39][CH2:40]2)=[C:29]([F:28])[CH:30]=1)(=[O:43])[CH3:42]

Participants

Conditions

Temperature: 50 °C

Procedure

To a solution of 2-bromo-5-cyano-benzoic acid (200 mg, 0.885 mmol) in DMF (3 ml) was added dropwise 1,1′-Carbonyldiimidazole (148 mg, 0.885 mmol). When the CO2 evolution ceased, the mixture was heated to 50° C. for 15 minutes. The mixture was cooled to room temperature. 1-(3-Fluoro-4-piperazin-1-yl-phenyl)-ethanone (198 mg, 0.885 mmol) was added portionwise. The mixture was stirred at room temperature for 1 hour. The solvent was removed in vacuo. The residue was dissolved in ethyl acetate. The solution was washed twice with water, dried over Na2SO4, filtered and the solvent was removed in vacuo. The crude oil was purified on SiO2 (Heptane/AcOEt 0%-30% (10 minutes)) to provide 3-[4-(4-acetyl-2-fluoro-phenyl)-piperazine-1-carbonyl]-4-bromo benzonitrile (185 mg, 49%) as white solid (M+ 430.3).

Workup

temperatureThe mixture was cooled to room temperature
customThe solvent was removed in vacuo
dissolutionThe residue was dissolved in ethyl acetate
washThe solution was washed twice with water
dry with materialdried over Na2SO4
filtrationfiltered
customthe solvent was removed in vacuo
customThe crude oil was purified on SiO2 (Heptane/AcOEt 0%-30% (10 minutes))

Sources & evidence

ORD record: ord-235def4a22684b68a2d4600700082894
Source dataset: uspto-grants-2008_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07462617B2

Reaction notes

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