Tetrahydrofuran → (7R,8aS)-2-benzyl-7-{[6-(trifluoromethyl)pyridin-3-yl]oxy}octahydropyrrolo[1,2-a]pyrazine
Reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][N:11]2[CH2:14][C@H:15]([OH:17])[CH2:16][C@H:10]2[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC(C)([O-])C.[K+].O1CCCC1.F[C:30]1[CH:31]=[CH:32][C:33]([C:36]([F:39])([F:38])[F:37])=[N:34][CH:35]=1>CS(C)=O>[CH2:1]([N:8]1[CH2:13][CH2:12][N:11]2[CH2:14][C@H:15]([O:17][C:30]3[CH:35]=[N:34][C:33]([C:36]([F:39])([F:38])[F:37])=[CH:32][CH:31]=3)[CH2:16][C@H:10]2[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Procedure
To a solution of (7R,8aS)-2-benzyloctahydropyrrolo[1,2-a]pyrazin-7-ol (Example 19D, 0.103 g, 0.443 mmol) in dimethyl sulfoxide (4 mL) was added a 1.0 M solution of potassium tert-butoxide in tetrahydrofuran (0.665 mL, 0.665 mmol), and the resulting suspension was stirred at room temperature for 5 minutes. 5-Fluoro-2-(trifluoromethyl)pyridine (0.137 g, 0.829 mmol) was added, and the reaction mixture was stirred at room temperature for 48 hours. The mixture was partitioned between ethyl acetate and water, and the organic extract was dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. Purification by column chromatography on silica gel using a solvent gradient of 0-95% ethyl acetate in hexane gave the titled compound. MS (APCI) m/z 378.4 (M+H)+.
Workup
- stirringthe reaction mixture was stirred at room temperature for 48 hours
- customThe mixture was partitioned between ethyl acetate and water
- extractionthe organic extract
- dry with materialwas dried over anhydrous sodium sulfate
- filtrationfiltered
- concentrationconcentrated in vacuo
- customPurification by column chromatography on silica gel using a solvent gradient of 0-95% ethyl acetate in hexane
Sources & evidence
- ORD record
- ord-07dd8f4442104a97b832f6e043d05c52
- Source dataset
- uspto-grants-2014_02
- Patent number
- US08648074B2
Reaction notes
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