Hydrochloric Acid → HCID 18415753, compound

Participants

Reaction Steps

3-Fluoromethoxybenzene (15.8 g, 125 mmol) was stirred at −78° C. in anh. THF (100 mL) and treated with n-BuLi (50 mL, 2.5M hexanes soln., 125 mmol) over 5 min. After stirring below −70° C. for 4 hours, the mixture was treated with cyclopent-3-enecarboxylic acid methoxy-methyl-amide (18.4 g, 119 mmol) dropwise over ˜¼ hour. The mixture was stirred below −70° C. for 1 hour, and then allowed to warm to ambient temperature over ˜1 hour. The mixture was poured into 1N aq. HCl soln. (200 mL) and shaken. The layers were separated and the aq. layer extracted with EtOAc (3×100 mL). The organic layer was washed with H2O (50 mL), sat. aq. NaHCO3 soln. (100 mL), and brine (50 mL), dried (Na2SO4), filtered through a Silica plug and concentrated to an oil (21.0 g, 76%). (TLC 30% EtOAc/hexanes Rf 0.43). GCMS m/e 220 (M+). This material was converted to the title compound by the methods described in Example 2C-G and Example 1G. (TLC 10% MeOH/CH2Cl2 (NH3) Rf 0.20). 1H NMR (CD3OD) δ 7.24 (m, 1H), 7.01 (m, 2H), 3.36 (d, J=13.0 Hz, 1H), 3.33-3.10 (m, 5H), 2.90 (d, J=18.5 Hz, 1H), 2.60 (m, 1H), 2.13 (AB d, J=13.0 Hz, 1 H), 1.97 (AB d, J=13.0 Hz, 1H). mp 240-241° C.

Provenance & Evidence