Reaktion #689260

Reaktionsgleichung

3,5-difluoro phenylboronic acid

tert-butyl 6-bromonicotinate

→

title compound

Ausbeute 93.0%

tert-butyl 6-(3,5-difluorophenyl)nicotinate

Ausbeute 93.0%

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigethe mixture was evacuated 3× with N2
2. 2
   workup.DISSOLUTIONThe solids were dissolved in 50 mL of DMF
3. 3
   workup.ADDITIONfollowed by addition of 11 mL of 2 M cesium carbonate
4. 4
   TemperaturThe mixture was cooled to rt
5. 5
   workup.ADDITIONpoured into a separatory funnel
6. 6
   workup.ADDITIONfollowed by addition of EtOAc and water (1×200 mL)
7. 7
   SonstigeThe layers were separated
8. 8
   Extraktionthe organic extract
9. 9
   Waschenwashed with brine (1×200 mL), dried MgSO4
10. 10
    Filtrationfiltered
11. 11
    Einengenconcentrated
12. 12
    Sonstigeto afford an orange oil
13. 13
    SonstigeThe crude mixture was purified by silica gel column chromatography on Biotage (silica, 2-10% EtOAc in Heptane)-ca 2.5 L

Vorschrift

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).

Quelle