Reaction Steps
To the solution of (2S,6S,13aS,14aR,16aS,Z)-ethyl 6-((tert-butoxycarbonyl) amino)-9′-methoxy-1′,5,16-trioxo-5′-(trifluoromethyl)-1′,2′,3,5,6,7,8,9,10,11,13a,14,14a,15, 16,16a-hexadecahydro-1H-spiro[cyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecine-2,3′-pyrano[2,3-c]quinoline]-14a-carboxylate (2923 mg, 3.85 mmol) in THF (26 ml) was added 1.4M of MeMgBr solution in THF (11.01 ml, 15.41 mmol) at −25° C. and stirred at −25° C. for 20 min. TLC and LC-MS indicated that the major was product (about 50%) and starting material. Then the reaction was quenched with 1N HCl to pH=5-6 (about 12 ml 1N HCl), and diluted with EtOAc (40 ml). The layers were separated, and the aq. layer was extracted again with EtOAc (25 ml×2). The organic layers were combined and washed with brine, dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by column chromatography on silica gel (120 g, gold column), eluting with 100% hexane for 400 ml, gradient to 35% of acetone to give 1430 mg of starting material and 1130 mg of (2S,6S,13aS,14aR,16aS,Z)-ethyl 6-((tert -butoxycarbonyl)amino)-1′-hydroxy-9′-methoxy-1′-methyl-5,16-dioxo-5′-(trifluoromethyl)-1′,2′,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a-hexadecahydro-1H-spiro[cyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecine-2,3′-pyrano[2,3-c]quinoline]-14a-carboxylate as a light yellow solid. m/z=775.4 (M+1)
