Pyrrolidine → 1-(5-chloro-2-nitrophenyl)pyrrolidine
Reaction equation
[NH:1]1[CH2:5][CH2:4][CH2:3][CH2:2]1.[Cl:6][C:7]1[CH:12]=[CH:11][C:10]([N+:13]([O-:15])=[O:14])=[C:9](F)[CH:8]=1>CS(C)=O>[Cl:6][C:7]1[CH:8]=[CH:9][C:10]([N+:13]([O-:15])=[O:14])=[C:11]([N:1]2[CH2:5][CH2:4][CH2:3][CH2:2]2)[CH:12]=1Participants
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 80 °C
Procedure
Add pyrrolidine (0.97 g, 13.67 mmol) to a solution of 4-chloro-2-fluoro-1-nitrobenzene (2 g, 11.40 mmol) in 8 mL anhydrous DMSO under N2. Stir the reaction mixture at 80° C. for 1 h. Cool the mixture, pour into ice-H2O and extract with Et2O (3×30 mL). Wash the organic phase with water and brine, dry over MgSO4, filter, and concentrate. Chromatograph the residue on silica gel using hex/EtOAc 9:1 as eluent to afford 2.29 g (89%) of 1-(5-chloro-2-nitro-phenyl)-pyrrolidine as a yellow solid. Add tin chloride (10 g, 44.15 mmol) to a solution of 1-(5-chloro-2-nitrophenyl)pyrrolidine (2 g, 8.83 mmol) in 25 mL of EtOH under nitrogen. Heat the reaction mixture at 70° C. for 3 h. After cooling, pour the mixture into ice-water, basify (pH=9) with NH4OH, and extract with EtOAc (3×100 mL). Dry the organic phase over MgSO4, concentrate, and purify the residue by silica gel chromatography using hex/EtOAc 8:2 as eluent to obtain 1.56 g (88%) of 1-(2-amino-5-chlorophenyl)pyrrolidine as an oil.
Workup
- temperatureCool the mixture
- extractionextract with Et2O (3×30 mL)
- washWash the organic phase with water and brine
- dry with materialdry over MgSO4
- filtrationfilter
- concentrationconcentrate
Sources & evidence
- ORD record
- ord-ed724ae859364ede807cac4d691790f9
- Source dataset
- uspto-grants-2008_11
- Patent number
- US07449477B2
Reaction notes
Loading…