反应详情

温度

70 °C

tert-butyl (S)-1-((S)-5-((6-bromo-2-methoxynaphthalen-1-yl)methyl)-4-oxo-2′,3′,4,5,5′,6′-hexahydro-3H-spiro[benzo[b][1,4]oxazepine-2,4′-pyran]-3-ylamino)-1-oxopropan-2-yl(methyl)carbamate (0.17 g, 249 μmol, Eq: 1.00), Pd(OAc)2 (2.24 mg, 9.96 μmol, Eq: 0.04) and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (Xantphos) (11.5 mg, 19.9 μmol, Eq: 0.08) were combined in a 5 mL microwave tube, the vessel was evacuated and purged with N2. MeOH (79.8 mg, 101 μl, 2.49 mmol, Eq: 10) and TEA (0.5 mL) were added, the vessel was purged with CO gas for approximately 30 sec and placed in an oil bath heated to 70° C. After 18 h, the mixture was cooled, diluted with EtOAc, washed with 1 N HCl, H2O, and brine. The organic mixture was dried over Na2SO4, concentrated and the residue purified by flash chromatography to afford methyl 5-(((S)-3-((S)-2-(tert-butoxycarbonyl (methyl)amino)propanamido)-4-oxo-2′,3′,5′,6′-tetrahydro-3H-spiro[benzo[b][1,4]oxazepine-2,4′-pyran]-5 (4H)-yl)methyl)-6-methoxy-2-naphthoate (110.5 mg, 67% as a light yellow foam.) MS m/z 662.3 (MH+)

1. customthe vessel was evacuated
2. custompurged with N2
3. customthe vessel was purged with CO gas for approximately 30 sec
4. customplaced in an oil bath
5. temperaturethe mixture was cooled
6. additiondiluted with EtOAc
7. washwashed with 1 N HCl, H2O, and brine
8. dry with materialThe organic mixture was dried over Na2SO4
9. concentrationconcentrated
10. customthe residue purified by flash chromatography