Cesium carbonate → Methyl 4-[4'-(formylamino)-1,1'-biphenyl-4-yl]-2,2-dimethyl-4-oxobutanoate

温度

80 °C

To a 2-L three-necked round-bottomed flask, were charged 4-iodoformanilide (30.0 g, 121 mmol, 1.0 eq), bis(pinacolato)diboron (30.8 g, 121 mmol, 1.0 eq), palladium acetate (0.82 g, 3.6 mmol, 3 mol %), potassium acetate (35.70 g, 364.3 mmol), and 500 mL N,N-dimethylformamide. The mixture was degassed by gently bubbling argon through the solution for 30 minutes at rt. The mixture was then heated at 80° C. under argon until the reaction was complete (2-3 hours). After the mixture was cooled to rt, methyl 4-(4-bromophenyl)-2,2-dimethyl-4-oxobutanoate (36.3 g, 121 mmol), cesium carbonate (59.4 g, 182 mmol), and palladium tetrakistriphenylphosphine (4.2 g, 3.6 mmol, 3 mol %) were added. The reaction mixture was then heated at 80° C. overnight under argon. The mixture was cooled to rt, and slowly diluted with water (1.5 L), which caused solid material to precipitate. The solids were removed by filtration, and washed with 500 mL water. Then the solids were dissolved in 500 mL methylene chloride, and black particles were removed by passing the solution through a pad of Celite®. The filtrate was washed with 150 mL water (2×). After the solution was dried over sodium sulfate, the solution was concentrated under reduced pressure to afford a dark, brown residue. The residue was stirred in ethyl acetate (200 mL) and hexane (200 mL) for 1 h. After filtration and drying, methyl 4-[4′-(formylamino)-1,1′-biphenyl-4-yl]-2,2-dimethyl-4-oxobutanoate was obtained as a yellow solid (28.0 g, 68%). 1H NMR (CDCl3) δ 8.42 (d, J=2 Hz, 1H), 7.98 (d, J=8 Hz, 2H), 7.62 (m, 6H), 3.70 (s, 3H), 3.33 (s, 2H), 1.35 (s, 6H) and 40% tautomer; ESI-MS m/z 340.1 (MH+).

1. customThe mixture was degassed by gently bubbling argon through the solution for 30 minutes at rt
2. custom(2-3 hours)
3. temperatureAfter the mixture was cooled to rt
4. temperatureThe reaction mixture was then heated at 80° C. overnight under argon
5. temperatureThe mixture was cooled to rt
6. customto precipitate
7. customThe solids were removed by filtration
8. washwashed with 500 mL water
9. dissolutionThen the solids were dissolved in 500 mL methylene chloride
10. customblack particles were removed
11. washThe filtrate was washed with 150 mL water (2×)
12. dry with materialAfter the solution was dried over sodium sulfate
13. concentrationthe solution was concentrated under reduced pressure
14. customto afford a dark, brown residue
15. filtrationAfter filtration
16. customdrying

ORDレコード

ord-5219abd4d8ba4e25a4eb0a52cf8c7b5f

出典データセット

uspto-grants-2011_06

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07968576B2