3-Bromo-2-fluoroanisole

At room temperature, add 20 mL of toluene, compound 3-2 (4.8 g, 23.18 mmoL), Tris (dibenzylideneacetone) dipalladium (0.28g, 0.31mmoL), Tris (o-methylphenyl) phosphorus (0.19g, 0.62mmoL), replaced with nitrogen three times, The temperature was raised to 60 to 70 C. Add the toluene solution of compound 2 in the three-necked bottle R1 dropwise, After the dropwise addition, keep it at 60 70 for 1h;The reaction solution was filtered through celite, and the filtrates were combined and washed with 20 mL of water.It was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated in vacuo to about 20 mL at 50 C, and cooled to 20-30 C. 160 mL of n-heptane was added dropwise to precipitate a solid, which was filtered to obtain a off-white solid, without further drying One-step synthesis2) Add 20mL of N, N-dimethylacetamide at room temperature, add compound 3-2 (5.3g, 25.70mmoL), tris (dibenzylideneacetone) dipalladium (0.43g, 0.46mmoL), Tris (o-methylphenyl) phosphorus (0.28g, 0.93mmoL), replaced with nitrogen three times, and warmed to 60-70 C. The N, N-dimethylacetamide solution of compound 2-1 in the three-necked flask was added dropwise. After the dropwise addition was completed, the temperature was maintained at 60-70 C for 3 hours.3) Add 100 mL of dichloromethane, filter the reaction solution through diatomaceous earth, combine the filtrates, concentrate under vacuum at 50 C until there are no obvious droplets, lower the temperature to 20-30 C, add 120 mL of water dropwise, precipitate a solid, and filter to obtain a off-white solid. Dry at 50-60 C. The crude product was heated to 60-65 C in ethanol for 0.6h, slowly cooled to 10-20 C for crystallization, and filtered to dry to obtain 8.7g of pure white compound 4 with a purity of 99.0% and a yield of 87%.A 250ml three-necked flask was charged with 5 g (24.4 mmol) of 2-fluoro-3-methoxy-bromobenzene, 13.5 g (103.74 mmol) of ethyl acetoacetate, 55ml of dimethyl sulfoxide, L-proline 1.12 g (9.76 mmol), 930 mg (4.88 mmol) of cuprous iodide, Under the protection of nitrogen, 32 g (97.6 mmol) of cesium carbonate was added, and the reaction was kept at 60 to 70 C for 4 to 5 hours.Stop the reaction, add 40 ml of saturated ammonium chloride solution, stir to dissolve, add 40 ml * 2 ethyl acetate for extraction, combine the ethyl acetate layers, wash the layers with saturated brine, and perform column chromatography (mobile phase ethyl acetate: petroleum ether = 1:15)5.4 g (21.3 mmol) of compound I was obtained as a pale yellow oil with a yield of 87.2%.A compound of formula 6a (20.50 g, 100 mmol), 7a (15.62 g, 120 mmol) and dimethyl sulfoxide (102 mL) were added to a three-neck flask.After stirring and stirring, cuprous iodide (1.90 g, 10 mmol), L-valine (1.15 g, 10 mmol), potassium carbonate (27.64 g, 200 mmol), Vacuum switching nitrogen 3 times, The temperature is raised to 45 to 50 C for 6 to 8 hours.After completion of the reaction, the reaction was quenched by the addition of ammonium chloride solution (204 mL), and extracted with ethyl acetate (102 mL), and the organic phase was combined and washed with saturated brine.Then, dry anhydrous sodium sulfate, concentrated to remove some solvent under reduced pressure, add petroleum ether to be beaten, filter, collect solids and dry to produce Product 8a (21.66 g, 74%).

Molecular Weight:205.02
XLogP3:2.7
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:203.95861
Monoisotopic Mass:203.95861
Topological Polar Surface Area:9.2
Heavy Atom Count:10
Complexity:110
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes