تفاعل #2286393

معادلة التفاعل

di(tert-butyl) 2-bromo-1,3-thiazol-5-ylimidodicarbonate

fluoropyridine boronic acid

ethanol

K2CO3

→

desired product

المردود 73.0%

di(tert-butyl) 2-(5-fluoropyridin-3-yl)-1,3-thiazol-5-ylimidodicarbonate

المردود 73.0%

المذيبات

toluene

ظروف التفاعل

المعالجة

1. 1
   أخرىThe flask was fitted with a reflux condenser
2. 2
   درجة الحرارةwas heated to reflux
3. 3
   درجة الحرارةthe reaction was cooled in an ice bath
4. 4
   أخرىpartitioned between aqueous saturated NaHCO3 and ethyl acetate
5. 5
   أخرىThe layers were separated
6. 6
   استخلاصthe aqueous layer was extracted once with ethyl acetate
7. 7
   غسيلThe combined organics were washed once with brine
8. 8
   تجفيفdried over MgSO4
9. 9
   ترشيحfiltered
10. 10
    تركيزconcentrated
11. 11
    أخرىThis solid was triturated with 20% ethyl acetate/hexanes
12. 12
    ترشيحThe solids were filtered off
13. 13
    أخرىthe filtrate evaporated
14. 14
    أخرىto provide a residue which
15. 15
    أخرىwas purified via silica gel column chromatography (0 to 100% ethyl acetate/hexanes)

الإجراء التجريبي

To a 3-neck round bottom flask was added fluoropyridine boronic acid (4.55 g, 32.3 mmol), ethanol (54 mL), and aqueous K2CO3 solution (27 mL, 2.0 M, 53.8 mmol), followed by 50 mL toluene. To this mixture was added di(tert-butyl) 2-bromo-1,3-thiazol-5-ylimidodicarbonate (10.2 g, 26.9 mmol). Next, tetrakis(triphenylphosphine)palladium(0) (6.2 g, 5.4 mmol) was added in one portion. The flask was fitted with a reflux condenser and was heated to reflux. After 45 minutes, the reaction was cooled in an ice bath and partitioned between aqueous saturated NaHCO3 and ethyl acetate. The layers were separated and the aqueous layer was extracted once with ethyl acetate. The combined organics were washed once with brine, dried over MgSO4, filtered, and then concentrated. This solid was triturated with 20% ethyl acetate/hexanes. The solids were filtered off and the filtrate evaporated to provide a residue which was purified via silica gel column chromatography (0 to 100% ethyl acetate/hexanes) to afford the desired product as an off-white solid (7.74 g, 73% yield): mp 94-96° C.; 1H NMR (300 MHz, CDCl3) δ 8.91 (app t, J=1.3 Hz, 1H), 8.52 (d, J=3.0 Hz, 1H), 7.96 (ddd, J=9.2, 3.0, 1.8 Hz, 1H), 7.66 (s, 1H), 1.48 (s, 18H); ESIMS m/z 396 (M+1).

المصدر