Hydrochloric Acid → HCID 69002504, compound

Participants

Reaction Conditions

Reaction Steps

To a 25 mL press resistant vial which contained a solution of (R)-2-(4-Hydroxy-phenoxymethyl)-pyrrolidine-1-carboxylic acid tert-butyl ester 2 (293 mg, 1 mmol) and the product from step 1 (340 mg, 1.5 mmol) in anhydrous dioxane (8 mL) were added cesium carbonate (450 mg, 2.5 mmol) and N,N-dimethylglycine.HCl (40 mg, 0.0.24 mmol) at rt. The reaction mixture was flushed with argon and copper (I) iodide (20 mg, 0.1 mmol) was added. The vial was sealed and the reaction mixture was stirred at 98° C. for 72 h. After cooled to rt, the mixture was poured onto 100 mL ice-water solution and this solution was extracted with EtOAc (3×30 mL). The combined organic layers were washed with water (2×30 mL), brine (30 mL) and dried over anhydrous Na2SO4. The solvent was removed under vacuo to obtain the crude product which was purified by silica gel flash chromatography to yield the title product, (260 mg, 75%); LCMS; 93%, ESI+ Calcd: 434.5, found m/z: 335.6 (M+1-boc); 1H NMR (400 MHz, CDCl3); δ 1.33-1.39 (m, 2H), 1.47 (s, 9H), 1.66-1.68 (m, 2H), 1.81-2.10 (m, 4H), 3.30-3.45 (m, 2H), 3.75-4.21 (m, 3H), 6.90 (d, J 9.2 Hz, 2H), 6.91-6.94 (m, 2H), 7.23 (d, J=8.4 Hz, 2H), 7.24-7.27 (m, 2H)

Provenance & Evidence