1-Bromo-3-chloropropane → (1S,5R)-3-(3-chloropropyl)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hexane
Reaction equation
[F:1][C:2]([F:16])([F:15])[C:3]1[CH:8]=[CH:7][C:6]([C@:9]23[CH2:14][C@H:13]2[CH2:12][NH:11][CH2:10]3)=[CH:5][CH:4]=1.Br[CH2:18][CH2:19][CH2:20][Cl:21]>C1COCC1.CCN(C(C)C)C(C)C.CCOC(C)=O>[Cl:21][CH2:20][CH2:19][CH2:18][N:11]1[CH2:12][C@H:13]2[C@:9]([C:6]3[CH:5]=[CH:4][C:3]([C:2]([F:1])([F:15])[F:16])=[CH:8][CH:7]=3)([CH2:14]2)[CH2:10]1Participants
6
Reactant 2
Product 1
Reagents, catalysts & solvents 3
Procedure
To a solution of (1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hexane (Prep4, 1.00 g) in dry THF (5 mL), DIPEA (2.4 mL) and 1-bromo-3-chloropropane (3.7 mL) were added and the resulting mixture was heated at reflux for 3 hours. After cooling at room temperature it was diluted with EtOAc (30 mL) washed twice with a saturated solution of NH4Cl in water (20 mL) and once with a saturated aqueous NaHCO3 solution (20 mL), dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified by silica gel chromatography eluting with cyclohexane/EtOAc 7:3 to give the title compound as a colourless oil (1.26 g).
Workup
- temperaturethe resulting mixture was heated
- temperatureat reflux for 3 hours
- washwashed twice with a saturated solution of NH4Cl in water (20 mL) and once with a saturated aqueous NaHCO3 solution (20 mL)
- dry with materialdried over anhydrous Na2SO4
- concentrationconcentrated under reduced pressure
- customThe crude product was purified by silica gel chromatography
- washeluting with cyclohexane/EtOAc 7:3
Sources & evidence
- ORD record
- ord-1dcf39d0bd4d4414bdb081cd9d298df5
- Source dataset
- uspto-grants-2012_05
- Patent number
- US08178549B2
Reaction notes
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