[Br:1][C:2]1[CH:3]=[C:4]([N:12]2[CH2:16][CH2:15][CH2:14][CH2:13]2)[CH:5]=[C:6]([O:8][CH2:9]OC)[CH:7]=1.Cl.[OH-].[NH4+].[C:20]([O-])([O-])=O.[K+].[K+].C(I)C>C(Cl)Cl.CO.CN(C=O)C>[Br:1][C:2]1[CH:3]=[C:4]([N:12]2[CH2:16][CH2:15][CH2:14][CH2:13]2)[CH:5]=[C:6]([O:8][CH2:9][CH3:20])[CH:7]=1A flask was charged with 1-(3-bromo-5-methoxymethoxy-phenyl)-pyrrolidine (206 mg, 0.72 mmol) and a solution of 10% ethanolic hydrogen chloride (5 ml, dry) was added. The flask was capped and stirred for 45 minutes. The volatile material was stripped (rotovap) and methylene chloride (10 ml) was added. This was again stripped. The remainder was taken up in methylene chloride (10 ml). To this stirred material was added a 5% solution of ammonium hydroxide in methanol (20 drops). This material was stripped and the procedure repeated once more. The stripped remainder was taken up in dry DMF (3 ml) and K2CO3 (348 mg, 2.52 mmol) was added. Ethyl iodide (0.07 ml, 0.9 mmol) was added and the mixture was capped and stirred for 2.5 hours. Additional ethyl iodide (0.15 ml, 1.9 mmol) was added and the material was capped and heated (60° C.) over night. Ethyl iodide (0.15 ml, 1.9 mmol) was again added and the mixture capped and heated (100° C.) for 12 hours. The volatiles were removed (rotovap/pump) and the remainder was taken up in water (25 ml) and ethyl acetate (25 ml) and the material shaken in a separtatory funnel. The organic phase was collected and the aqueous phase was back extracted with ethyl acetate (2×20 ml), the organics combined, dried (MgSO4), filtered and stripped to provide a crude oil. The oil was purified by preparative TLC using 7% EtOAc in hexanes as eluant to provide 86 mg of 1-(3-bromo-5-ethoxy-phenyl)-pyrrolidine as a golden brown semi-viscous oil.
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