Ethyl 1-azabicyclo(2.2.2)octane-4-carboxylate → 1-Azabicyclo[2.2.2]oct-4-yl[bis(4-fluorophenyl)]methanol
Reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([Mg]Br)=[CH:4][CH:3]=1.[N:10]12[CH2:17][CH2:16][C:13]([C:18]([O:20]CC)=O)([CH2:14][CH2:15]1)[CH2:12][CH2:11]2>C1COCC1>[N:10]12[CH2:11][CH2:12][C:13]([C:18]([C:5]3[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=3)([C:5]3[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=3)[OH:20])([CH2:14][CH2:15]1)[CH2:16][CH2:17]2Participants
4
Procedure
A solution of 4-fluorophenylmagnesiumbromide (1.0 M in THF, 4.4 mL, 4.4 mmol) was chilled down to 0° C. under Ar. Ethyl 1-azabicyclo[2.2.2]octane-4-carboxylate (0.1973 g, 1.08 mmol) in THF (4 mL) was slowly added to the reaction mixture at 0° C. over 20 min. The reaction was allowed to warm up to room temperature and then heated at 60° C. for 16 h. The reaction was chilled in an ice bath, quenched with saturated NH4Cl, and concentrated under vacuum. The resulting residue was treated with H2O and extracted with EtOAc. The combined organic layers were dried with MgSO4, filtered, and concentrated under vacuum to yield the desired product (0.3152 g, 88.9%). EI-MS m/z 330 (M+H+) Rt (1.65 min).
Workup
- temperatureheated at 60° C. for 16 h
- temperatureThe reaction was chilled in an ice bath
- customquenched with saturated NH4Cl
- concentrationconcentrated under vacuum
- additionThe resulting residue was treated with H2O
- extractionextracted with EtOAc
- dry with materialThe combined organic layers were dried with MgSO4
- filtrationfiltered
- concentrationconcentrated under vacuum
Sources & evidence
- ORD record
- ord-74751e52793440a9b62803832abd1dae
- Source dataset
- uspto-grants-2015_06
- Patent number
- US09045469B2
Reaction notes
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