Cesium carbonate → Tert-butyl (3-bromo-2-chloro-5-(difluoromethoxy)phenyl)carbamate
Reaction equation
Br[C:2]1[CH:7]=[C:6]([O:8][CH:9]([F:11])[F:10])[CH:5]=[C:4]([Br:12])[C:3]=1[Cl:13].[C:14](=[O:21])([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])[NH2:15].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Br:12][C:4]1[C:3]([Cl:13])=[C:2]([NH:15][C:14](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])[CH:7]=[C:6]([O:8][CH:9]([F:11])[F:10])[CH:5]=1Participants
7
Reactant 4
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- 105 °C
Procedure
1,3-Dibromo-2-chloro-5-(difluoromethoxy)benzene (4.38 g, 13.02 mmol), tert-butyl carbamate (1.220 g, 10.42 mmol), palladium(ii) acetate (0.146 g, 0.651 mmol), XANTPHOS (0.942 g, 1.628 mmol) and cesium carbonate (16.97 g, 52.1 mmol) were suspended in dioxane (87 ml) at room temperature. The reaction mixture was degassed through evacuating under vacuum and backfilling with N2 (Repeated 3×) and heated to 105° C. for 2 h. After cooling to room temperature, the reaction mixture was diluted with EtOAc, filtered through celite and concentrated. Column chromatography (120 g SiO2, 0 to 20% EtOAc-hexane gradient elution) afforded tert-butyl (3-bromo-2-chloro-5-(difluoromethoxy)phenyl)carbamate (2.79 g).
Workup
- customThe reaction mixture was degassed
- customthrough evacuating under vacuum and backfilling with N2 (Repeated 3×)
- temperatureAfter cooling to room temperature
- additionthe reaction mixture was diluted with EtOAc
- filtrationfiltered through celite and
- concentrationconcentrated
- washColumn chromatography (120 g SiO2, 0 to 20% EtOAc-hexane gradient elution)
Sources & evidence
- ORD record
- ord-a73b29f655f04703a8bebe5a112df052
- Source dataset
- uspto-grants-2016_03
- Patent number
- US09273057B2
Reaction notes
Loading…