[CH3:1][N:2]1[C@H:6]([CH2:7][O:8][C:9]2[CH:10]=[N:11][CH:12]=[CH:13][CH:14]=2)[CH2:5][CH2:4][C:3]1=O.[CH3:16][Li].[H-].[Al+3].[Li+].[H-].[H-].[H-].[OH-].[Na+]>O1CCCC1.C(OCC)C.O>[CH3:1][N:2]1[C@H:3]([CH3:16])[CH2:4][CH2:5][C@H:6]1[CH2:7][O:8][C:9]1[CH:10]=[N:11][CH:12]=[CH:13][CH:14]=1To a stirred solution of 0.121 g (0.587 mmole) (S)-1-Methyl-5-((pyridin-3-yloxy)methyl)pyrrolidin-2-one in 10 ml of dry tetrahydrofuran under argon atmosphere at ice cooling, 1.10 ml (1.76 mmole) of 1.6M methyllithium solution in diethyl ether was added drop by drop for 5 minutes and stirred for 5 minutes under ice cooling, and then at room temperature for 1 hour. To this reaction mixture at room temperature and while stirring, 2.95 ml (2.95 mmole) 1M lithium aluminum hydride solution in tetrahydrofuran was added in 3 minutes and stirred for 1 hour. First 0.29 ml of 10% sodium hydroxide aqueous solution was added drop by drop and after 10 minutes stirring 0.29 ml water was added and stirred for 2 hours. The precipitate was filtered and it was washed with 5×5 ml of ethyl acetate, the combined organic solutions were evaporated at 35° C. in good vacuum. The residue (0.102 g) was separated with column chromatography on 10 g silica gel with cyclohexane-diethylamine (80-20, v/v) giving the more polar 3-(((2S,5R)-1,5-dimethylpyrrolidin-2-yl)methoxy)pyridine in pure form (5.42 mg, 4.5%). From the less polar fractions with column chromatography on 2 g silica gel we got the pure 3-(((2S,5S)-1,5-Dimethylpyrrolidin-2-yl)methoxy)pyridine (1.12 mg, 9%) isomer. The cis and trans configurations of the substituents at the 1 and 5 positions of the pyrrolidine ring were determined by nuclear Overhauser experiments.
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