tert-Butyl piperazine-1-carboxylate → HCID 69418446, compound
Reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[F:12])[C:8](OS(C(F)(F)F)(=O)=O)=[CH:7][CH:6]=[CH:5]2.[C:21]([N:28]1[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]1)([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22].C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1.CC([O-])(C)C.[Na+]>C1(C)C=CC=CC=1.CC([O-])=O.CC([O-])=O.[Pd+2]>[C:24]([O:23][C:21]([N:28]1[CH2:33][CH2:32][N:31]([C:8]2[C:9]3[C:4](=[CH:3][C:2]([F:1])=[C:11]([F:12])[CH:10]=3)[CH:5]=[CH:6][CH:7]=2)[CH2:30][CH2:29]1)=[O:22])([CH3:27])([CH3:25])[CH3:26]Participants
7
Conditions
- Temperature
- 80 °C
Procedure
A third intermediate compound, 1-(6,7-Difluoro-naphthalen-1-yl)-piperazine, was produced as follows: Nitrogen gas was bubbled through a solution of trifluoro-methanesulfonic acid 6,7-difluoro-naphthalen-1-yl ester (4.38 g, 14.04 mmol), 1-Boc-piperazine (3.18 g, 16.85 mmol), Pd(OAc)2 (0.31 g, 1.4 mmol) and 2-dicyclohexylphosphino biphenyl (0.49 g, 1.4 mmol) in toluene (40 mL) for 10 min. NaOtBu (1.89 g, 19.66 mmol) was added. The resulting mixture was heated at 80° C. for 2 h, cooled to RT, diluted with EtOAC (40 mL) and filtered through a pad of celite. The filtrate was concentrated and the residue was purified by chromatography on silica gel to give 4-(6,7-difluoro-naphthalen-1-yl)-piperazine-1-carboxylic acid tert-butyl ester.
Workup
- temperaturecooled to RT
- additiondiluted with EtOAC (40 mL)
- filtrationfiltered through a pad of celite
- concentrationThe filtrate was concentrated
- customthe residue was purified by chromatography on silica gel
Sources & evidence
- ORD record
- ord-5570103dff3648ce8bf1c1e0404da5d7
- Source dataset
- uspto-grants-2007_01
- Patent number
- US07160888B2
Reaction notes
Loading…