4,4'-Bis(1,1-dimethylethyl)-1,1'-biphenyl → 2-(3-Fluorophenyl)-2-methylpyrrolidine

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Reaction Conditions

Reaction Steps

In step 8-2, 3-chloro-N-(1-(3-fluorophenyl)ethylidene)propan-1-amine (8-1) (4.7 g, 22 mmol) was added at −78° C. to a solution of lithium granules (0.8 g, 110 mmol) and 4,4′-di-tert-butylbiphenyl (0.6 g, 2.2 mmol) in THF (40 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 increase to 20° C. Solids were then removed by filtration, the mother liquor was reduced using a rotary evaporator and the resulting residue was reconstituted in ethyl acetate. The organic was washed with 1N HCl (3×25 mL) and the aqueous layer extracted with ethyl acetate. The aqueous layer was neutralized with 1N NaOH solution and extracted with ethyl acetate (3×100 mL). The organic layer was dried with sodium sulfate and the solvent removed to yield 2-(3-fluorophenyl)-2-methylpyrrolidine (8-2) as a light yellow oil. m/z=180.3 [M+1].

Provenance & Evidence