Thionyl Chloride → tert-Butyl 4-(trifluoromethyl)-3',6'-dihydro-2,4'-bipyridine-1'(2'H)-carboxylate
Reaction equation
O[C:2]1([C:15]2[CH:20]=[C:19]([C:21]([F:24])([F:23])[F:22])[CH:18]=[CH:17][N:16]=2)[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]1.S(Cl)(Cl)=O>N1C=CC=CC=1>[C:11]([O:10][C:8]([N:5]1[CH2:4][CH:3]=[C:2]([C:15]2[CH:20]=[C:19]([C:21]([F:24])([F:23])[F:22])[CH:18]=[CH:17][N:16]=2)[CH2:7][CH2:6]1)=[O:9])([CH3:14])([CH3:12])[CH3:13]Participants
4
Procedure
To a solution of tert-butyl 4-hydroxy-4-[4-(trifluoromethyl)pyridin-2-yl]piperidine-1-carboxylate (2.00 g, 2.31 mmol) in pyridine (15.9 mL) cooled in an ice bath was slowly added thionyl chloride (0.84 mL, 12 mmol). The mixture was allowed to warm to room temperature and stirred overnight (17 h). The brown reaction mixture was quenched with ice water and extracted with methylene chloride three times. The combined extracts were dried (MgSO4), filtered, and concentrated. The residue was purified by flash chromatography on silica gel (0-10% B over 25 min. Bottle A=hexanes, Bottle B=EtOAc) to give 404 mg (53%) of desired product as light brown oil. LC-MS calculated for C16H19F3N2O2: (M+H) 329; found 273.1 (M-tBu+1).
Workup
- customThe brown reaction mixture was quenched with ice water
- extractionextracted with methylene chloride three times
- dry with materialThe combined extracts were dried (MgSO4)
- filtrationfiltered
- concentrationconcentrated
- customThe residue was purified by flash chromatography on silica gel (0-10% B over 25 min
Sources & evidence
- ORD record
- ord-3a736f3d7cd94e1d9d3d531416a6750b
- Source dataset
- uspto-grants-2013_10
- Patent number
- US08563582B2
Reaction notes
Loading…