Cesium carbonate → HCID 11856677, compound

Participants

Reaction Conditions

Reaction Steps

To (1S,5R)-6-[(4-hydroxyphenyl)sulfonyl]-1-methyl-6-azabicyclo[3.2.0]heptan-7-one (291 mg, 1.04 mmol) was added cesium carbonate (1.011 g, 2.70 mmol) and 4-(chloromethyl) -2-methylquinoline (498 mg, 2.18 mmol) in acetonitrile (2 mL), with DMF to aid solubility. This reaction was stirred at room temperature overnight with partial β-lactam hydrolysis being observed. Water was then added to the reaction mixture and it was heated in a microwave for 5 min at 150° C. The mixture was then diluted with ethyl acetate, washed with water and brine. The aqueous layers were acidified to pH 4 with 1 M HCl and then extracted with ethyl acetate. The combined organic extracts were dried over Na2SO4)] and concentrated to give an orange oil that was carried on without further purification. The orange oil was combined with BOP (500 mg, 1.13 mmol), hydroxylamine hydrochloride (179 mg, 2.56 mmol), and triethylamine (710 μL) in DMF (3 mL). This mixture was stirred at room temperature overnight, the solids were filtered and the filtrate was purified by HPLC eluting with a gradient of 15-100% MeCN/H2O (10 min) to give (1S,2R)-N-hydroxy-1-methyl-2-[({4-[(2-methylquinolin-4-yl)methoxy]phenyl}sulfonyl)amino]cyclopentanecarboxamide (107 mg, 0.228 mmol, 24%) as a colorless solid. LCMS (M−H): 1.72 min; 468.4; 1H NMR (400 MHz, DMSO-D6) δ ppm 1.07 (s, 3H) 1.41 (m, 3H) 1.54 (s, 1H) 1.99 (d, J=1.01 Hz, 1H) 2.60-2.70 (m, 3H) 3.13 (s, 1H) 5.72 (s, 2H) 7.27-7.36 (m, 2H) 7.53-7.65 (m, 2H) 7.73-7.85 (m, 2H) 7.98 (d, J=8.34 Hz, 1H) 8.10 (s, 1H).

Provenance & Evidence