Reaktion #689276

Reaktionsgleichung

2,5-difluoro phenylboronic acid

tert-butyl 6-bromonicotinate

→

desired product

Ausbeute 40.0%

tert-butyl 6-(2,5-difluorophenyl)nicotinate

Ausbeute 40.0%

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigethe mixture was evacuated 3× with N2
2. 2
   workup.DISSOLUTIONThe solids were dissolved in 25 mL of DMF
3. 3
   workup.ADDITIONfollowed by addition of 2.9 mL of 2 M cesium carbonate
4. 4
   TemperaturThe mixture was cooled to rt
5. 5
   workup.ADDITIONpoured into a sep
6. 6
   workup.ADDITIONfunnel, followed 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 chromatography (silica, 10% EtOAc:Heptane)

Vorschrift

To round-bottom flask was added 2,5-difluoro phenylboronic acid (306 mg, 1.94 mmol), palladium tetrakis(triphenylphosphine) (22.4 mg, 0.0194 mmol)) and tert-butyl 6-bromonicotinate (500 mg, 1.94 mmol) and the mixture was evacuated 3× with N2. The solids were dissolved in 25 mL of DMF, followed by addition of 2.9 mL of 2 M cesium carbonate. The resulting mixture was heated to ˜90° C. The mixture was cooled to rt and then poured into a sep. 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 chromatography (silica, 10% EtOAc:Heptane) to afford the desired product (224 mg, 40%). 1H NMR (400 MHz, DMSO-d6) □ ppm 9.07-9.19 (1H, m), 8.36 (1H, dd, J=8.2, 2.2 Hz), 7.99 (1H, dd, J=8.3, 1.8 Hz), 7.75-7.86 (1H, m), 7.36-7.52 (1H, m), 7.36-7.52 (2H, m), 1.59 (9H, s). LC/MS (M+H)=292.1 observed, 292.11 expected.

Quelle