Pivalic acid → HCID 58293638, compound
Reaction equation
Br[C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[C:4]([Cl:9])[CH:3]=1.[O:10]1[CH:14]=[CH:13][N:12]=[CH:11]1.C12(P(C34CC5CC(CC(C5)C3)C4)CCCC)CC3CC(CC(C3)C1)C2.C(O)(=O)C(C)(C)C.C(=O)([O-])[O-].[K+].[K+]>CC(N(C)C)=O.CCOC(C)=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:9][C:4]1[CH:3]=[C:2]([C:14]2[O:10][CH:11]=[N:12][CH:13]=2)[CH:8]=[CH:7][C:5]=1[NH2:6]Participants
Reactant 5
Product 1
Reagents, catalysts & solvents 3
Conditions
- Temperature
- 110 °C
Procedure
Palladium acetate (5.4 mg, 0.024 mmol) was added to a solution of 4-bromo-2-chloroaniline (0.1 g, 0.484 mmol), oxazole (0.064 mL, 0.969 mmol), di(1-adamantyl)-n-butylphosphine (0.017 g, 0.048 mmol), pivalic acid (0.020 g, 0.194 mmol) and potassium carbonate (0.201 g, 1.453 mmol) in DMA (2.4 mL). The reaction mixture was heated at 110° C. overnight before being diluted with EtOAc and quenched with water. The layers were separated and the aqueous layer was extracted with EtOAc. The combined organic layers were dried (Na2SO4), filtered and concentrated under reduced pressure. The crude mixture was purified via Biotage silica gel column chromatography eluting with (Cyclohexane/EtOAc 80/20 to 60/40) to give the title product as a white solid (35 mg, 37%). 1H NMR (500 MHz, CDCl3): δ 4.25 (br s, 2H), 6.82 (d, J=8.3 Hz, 1H), 7.20 (s, 1H), 7.38 (dd, J=8.3, 2.0 Hz, 1H), 7.58 (d, J=2.0 Hz, 1H), 7.87 (s, 1H).
Workup
- customquenched with water
- customThe layers were separated
- extractionthe aqueous layer was extracted with EtOAc
- dry with materialThe combined organic layers were dried (Na2SO4)
- filtrationfiltered
- concentrationconcentrated under reduced pressure
- customThe crude mixture was purified via Biotage silica gel column chromatography
- washeluting with (Cyclohexane/EtOAc 80/20 to 60/40)
Sources & evidence
- ORD record
- ord-532e275876574ae5a2fd99e935c8b657
- Source dataset
- uspto-grants-2016_06
- Patent number
- US09371319B2
Reaction notes
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