1,2-Difluoro-4-nitrobenzene → (3R,5S)-1-(2-Fluoro-4-nitrophenyl)-3,5-dimethylpiperazine

Reaction equation

[F:1][C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[CH:5]=[CH:4][C:3]=1[N:11]1[CH2:16][C@@H:15]([CH3:17])[NH:14][CH2:13][C@@H:12]1C.F[C:20]1C=CC([N+]([O-])=O)=CC=1F.C[C@H]1CNC[C@@H](C)N1>>[F:1][C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[CH:5]=[CH:4][C:3]=1[N:11]1[CH2:12][C@H:13]([CH3:20])[NH:14][C@H:15]([CH3:17])[CH2:16]1

Participants

Reactant 3

HCID 1230531,2-Difluoro-4-nitrobenzene

HCID 6950261rel-(2R,6S)-2,6-dimethylpiperazine

HCID 57664344Racemic-1-(2-fluoro-4-nitrophenyl)-trans-2,5-dimethylpiperazine

Product 1

HCID 57664386(3R,5S)-1-(2-Fluoro-4-nitrophenyl)-3,5-dimethylpiperazineYield 103%

Procedure

Crude 1-(2-fluoro-4-nitrophenyl)-cis-3,5-dimethylpiperazine (5.71 g, 103% recovery) is prepared according to the method described above for the synthesis of racemic-1-(2-fluoro-4-nitrophenyl)-trans-2,5-dimethylpiperazine by treatment of 1,2-difluoro-4-nitrobenzene (3.48 g, 21.8 mmol) with cis-2,6-dimethylpiperazine (2.50 g, 21.8 mmol). The crude product is used in the next step without chromatographic purification. LCMS-ESI (m/z): calcd for C12H16FN3O2, 253; [M+H]+ found, 254.