Carbon Dioxide → 3-fluoro-4-((5R,7S)-7-hydroxy-7-(4-(trifluoromethoxy)phenyl)-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)benzonitrile

Beteiligte Stoffe

Reaktionsbedingungen

Reaktionsschritte

To a solution of a 1.6 M n-BuLi solution in hexane (0.428 ml, 0.684 mmol) cooled in a dry ice and acetone bath was added a solution of 1-bromo-4-(trifluoromethoxy)benzene (0.046 ml, 0.311 mmol) in 1 mL THF. The yellow crude was stirred at −78° C. for 1 hr. This crude was cannulated to a solution of 3-fluoro-4-((R)-7-oxo-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-benzonitrile (75 mg, 0.311 mmol) in THF (1 mL) cooled to −78° C. The crude was slowly warmed to room temperature over 5 hrs. The crude was quenched with NH4Cl and diluted with EtOAc. The organic layer was washed with brine, dried over MgSO4, filtered, and concentrated. The crude was first purified via preparation plate using 5% (2M NH3 in MeOH)/CH2Cl2. The product was further purified using HPLC to give 19.8 mg of the entitled product as the major diastereomer. MS 404.2 (M+H); LCMS condition A, retention time 1.38 min. 1H NMR (400 MHz, CDCl3) δ ppm 2.94 (d, 1H), 3.26 (dd, 1H), 5.71 (d, 1H), 6.72 (br. s., 1H), 7.03-7.17 (m, 3H), 7.27-7.39 (m, 3H), 7.40-7.52 (m, 2H).

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