(R)-3-fluoro-4-(7-oxo-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)benzonitrile → tert-butyl 2-((5R,7S)-5-(4-cyano-2-fluorophenyl)-7-hydroxy-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-7-yl)acetate

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Reaction Steps

To a solution of (R)-3-fluoro-4-(7-oxo-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)benzonitrile (2.0 g, 8.29 mmol) in THF (40.8 mL) was added a solution of 0.5M (2-tert-butoxy-2-oxoethyl)zinc(II) chloride in THF (39.8 mL, 19.90 mmol). The crude was stirred at room temperature for 2 hrs. To the crude was added and additional 0.5M 2-tert-butoxy-2-oxoethyl)zinc(II) chloride solution in THF (16.6 mL, 8.29 mmol). The crude was stirred at room temperature for 0.5 hr. The crude was quenched with saturated NH4Cl and diluted in EtOAc. The organic layer was washed with brine, dried over MgSO4, filtered, and concentrated. The crude was purified via HPLC 15% to 40% MeCN/H2O, to give 365 mg of the entitled product as the major diastereomer. MS 358.2 (M+H), LCMS condition A, retention time 1.21 min. 1H NMR (400 MHz, CDCl3) δ ppm 1.44 (s, 9H), 2.66-2.74 (m, 1H), 2.76-2.90 (m, 2H), 3.05-3.17 (m, 1H), 5.69 (dd, 1H), 6.96 (s, 1H), 7.12 (t, 1H), 7.31-7.38 (m, 2H), 7.44 (d, 1H).

Provenance & Evidence