(3,5-Difluorophenyl)boronic acid → Tert-butyl 6-(3,5-difluorophenyl)nicotinate

温度

90 °C

To round-bottom flask was added 3,5-difluoro phenylboronic acid (1.84 g, 11.6 mmol), palladium tetrakis(triphenylphosphine) (89.5 mg, 0.08 mmol) and tert-butyl 6-bromonicotinate (2.0 g, 7.75 mmol) and the mixture was evacuated 3× with N2. The solids were dissolved in 50 mL of DMF, followed by addition of 11 mL of 2 M cesium carbonate. The resulting mixture was heated to ˜90° C. until no starting bromide material was apparent by HPLC. The mixture was cooled to rt and then poured into a separatory funnel, followed by addition of EtOAc and water (1×200 mL). The layers were separated and the organic extract washed with brine (1×200 mL), dried MgSO4, filtered and concentrated to afford an orange oil. The crude mixture was purified by silica gel column chromatography on Biotage (silica, 2-10% EtOAc in Heptane)-ca 2.5 L to afford the title compound 2.1 g (93%) as white solid. 1H NMR (400 MHz, DMSO-d6) □ ppm 9.10-9.14 (1H, m), 8.29-8.35 (1H, m), 8.20-8.25 (1H, m), 7.90 (2H, dd, J=9.0, 1.5 Hz), 7.42 (1H, s), 1.59 (9H, s).

1. customthe mixture was evacuated 3× with N2
2. dissolutionThe solids were dissolved in 50 mL of DMF
3. additionfollowed by addition of 11 mL of 2 M cesium carbonate
4. temperatureThe mixture was cooled to rt
5. additionpoured into a separatory funnel
6. additionfollowed by addition of EtOAc and water (1×200 mL)
7. customThe layers were separated
8. extractionthe organic extract
9. washwashed with brine (1×200 mL), dried MgSO4
10. filtrationfiltered
11. concentrationconcentrated
12. customto afford an orange oil
13. customThe crude mixture was purified by silica gel column chromatography on Biotage (silica, 2-10% EtOAc in Heptane)-ca 2.5 L

ORDレコード

ord-2c6e10c21cda40ad950ea232f974deec

出典データセット

uspto-grants-2011_03

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07902373B2