Hydrochloric Acid → 5-[4-(4-Fluoro-phenyl)-3-hydroxy-butyl]-1-[6-(2H-tetrazol-5-yl)-hexyl]-pyrrolidin-2-one

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Reaction Steps

Following the procedure described for Example 3, Step D, 7-{2-[4-(4-fluoro-phenyl)-3-hydroxy-butyl]-5-oxo-pyrrolidin-1-yl}-heptanenitrile (71 mg, 0.197 mmol) was reacted with azidotrimethylsilane (45 mg, 0.394 mmol) and dibutyltin oxide (5 mg, 0.02 mmol) in toluene (10 mL) heated under reflux for 16 h. Additional azidotrimethylsilane (200 mg) and dibutyltin oxide (50 mg) were added and the reaction mixture was heated under reflux for 5 h. The reaction mixture was acidified with 1N HCl to pH=2 (5 mL) and the aqueous solution was washed with EtOAc (4×10 mL). The combined organic solutions were dried (MgSO4), filtered, and concentrated. Purification by medium pressure chromatography (EtOAc to 39:1 EtOAc:MeOH to 19:1 EtOAc:MeOH) provided the title compound of Example 5A (39 mg). 1H NMR (CDCl3) 67 7.16 (m, 2H), 7.00 (m, 2H), 3.81 (m, 1H), 3.68 (m,1H), 3.53 (m, 1H), 2.99 (m, 3H), 2.80 (m, 1H), 2.68 (m, 1H), 2.47 (m, 2H), 2.20 (m, 1H), 1.88-1.22 (m, 14H); MS 404.3 (M+1); 402.3 (M−1).

Provenance & Evidence