1,2-Dichloroethane → HCID 9882812, compound

Participants

Reaction Steps

To a solution of ester 71 (300 mg, 1.25 mmol) in THF (18 mL) was added a solution of LiOH.H2O (262 mg, 6.24 mmol) in H2O (6 mL) and the suspension was stirred overnight. The mixture was then acidified with HCl (1 N) to pH 2 and then extracted with EtOAc (3×15 mL). The extracts were combined, washed with brine, dried over MgSO4, and filtered. Concentration under reduced pressure left a white solid (211 mg, 0.93 mmol, 75%). To a solution of this acid (109 mg, 0.48 mmol), EDC (111 mg, 0.58 mmol), and DMAP (5 mg) in CH2Cl2 (5 mL) was added aniline (49 μL, 0.53 mmol) and the reaction allowed to proceed overnight. The solution was partitioned between H2O (5 mL) and EtOAc (10 mL). The layers were separated, and the aqueous phase extracted with EtOAc (3×5 mL). The organic portions were combined, washed with brine, dried over MgSO4, and filtered. Evaporation under reduced pressure left a solid which was purified by preparative TLC (30% EtOAc/hexanes) with isolation of the least polar band by EtOAc extraction. The extract was concentrated to give 72 as a yellowish solid (92 mg, 0.31 mmol, 65%). TLC Rf 0.48 (50% EtOAc/hexanes); 1H-NMR (400 MHz, CDCl3) δ 7.51 (d, 2H), 7.32 (t, 2H), 7.10 (t, 1H), 2.72 (t, 2H), 2.36 (t, 2H), 1.72 (m, 4H), 1.40 (m, 4H); 19F NMR (? MHz, CDCl3) −78.40 (s, 3F); MS (APCI+) calcd for C15H19F3NO2 301, found 325 [M+Na]+.

Provenance & Evidence