Cl[CH2:2][CH2:3][CH2:4][N:5]=[CH:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([F:13])[CH:8]=1.[Li].C(C1C=CC(C2C=CC(C(C)(C)C)=CC=2)=CC=1)(C)(C)C>C1COCC1>[F:13][C:9]1[CH:8]=[C:7]([CH:6]2[CH2:2][CH2:3][CH2:4][NH:5]2)[CH:12]=[CH:11][CH:10]=1In step 9-2, 3-chloro-N-(3-fluorobenzylidene)propan-1-amine (9-1) (53 g, 266 mmol) was added at −78° C. to a solution of lithium granules (5.5 g, 800 mmol) and 4,4′-di-tert-butylbiphenyl (5.7 g, 21 mmol) in THF (50 mL) cooled to −78° C. The resulting solution was stirred at −78° C. for 2 hours then quenched with water and the temperature was allowed to rise up to 20° C. The solids were removed by filtration and the mother liquor was reduced using a rotary evaporator. The resulting residue was reconstituted in ethyl acetate, the organic washed with 1N HCl (3×25 mL) and the aqueous layer was extracted with ethyl acetate. The aqueous layer was then neutralized with 1N NaOH solution and the aqueous layer was extracted with ethyl acetate (3×100 mL). The organic layer was dried with sodium sulfate and the solvent was removed to yield 2-(3-fluorophenyl)pyrrolidine (9-2) as a light yellow oil. m/z=165.2 [M+1].
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