反应详情

To a solution of 3-methyl-3-((R)-4-methyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino)-azetidine-1-carboxylic acid tert-butyl ester (20 g, 49.8 mmol) in CH2Cl2 (240 mL) and MeOH (120 mL) was added tetra-n-butylammonium tribromide (24.02 g, 49.8 mmol) in portions and the reaction mixture was stirred for 4 h. Saturated aqueous Na2S2O3 solution (100 mL) and saturated aqueous NaHCO3 solution (50 mL) was added to quench the reaction. The aqueous solution was extracted with CH2Cl2 (3×50 mL). The combined organic phase was dried over anhydrous Na2SO4 and filtered. The filtrate was concentrated in vacuo and the residue was purified by column chromatography on silica gel (eluting with 20-50% EtOAc in petroleum ether) to give 3-((R)-7-bromo-4-methyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino)-3-methyl-azetidine-1-carboxylic acid tert-butyl ester (20 g, 84%) as a yellow solid. 1H NMR (CDCl3, 400 MHz): δ 8.68 (brs, 1H), 7.14 (s, 1H), 4.63-4.57 (m, 1H), 4.56-4.45 (m, 2H), 4.34 (s, 1H), 4.08-4.01 (m, 2H), 3.96-3.90 (m, 2H), 1.62 (s, 3H), 1.51-1.45 (m, 12H). LCMS (Table 1, Method 25) Rt=0.867 min; MS m/z: 482 [M+H+2]+& 480 [M+H]+. SFC (Table 1, Method 31) Rt=5.402 min.

1. customto quench
2. customthe reaction
3. extractionThe aqueous solution was extracted with CH2Cl2 (3×50 mL)
4. dry with materialThe combined organic phase was dried over anhydrous Na2SO4
5. filtrationfiltered
6. concentrationThe filtrate was concentrated in vacuo
7. customthe residue was purified by column chromatography on silica gel (eluting with 20-50% EtOAc in petroleum ether)