反应详情

温度

80 °C

In a glove box, to a 40 mL I-Chem vial equipped with a stir bar and containing 2-iodo-4-bromo-5-methoxy-1-methoxymethoxybenzene (500 mg, 1.34 mmol) was added potassium acetate (395 mg, 4.02 mmol), bis(neopentylglycolato)diboron (363 mg, 1.61 mmol) and PdCl2(dppf) (33 mg, 0.040 mmol). The vial was sealed with a septum cap and then removed from the glove box. To the vial was then added DMSO (11 mL) and the resulting mixture was sealed under an atmosphere of argon and stirred at 80° C. for 13 h. The mixture was then allowed to cool to 23° C. and 1 M aq. NaOH was added (0.9 mL, 0.9 mmol). The mixture was stirred at 23° C. for 10 minutes and then diluted with saturated aq. NH4Cl (50 mL), water (50 mL), and Et2O (100 mL). The layers were separated and the organic phase was washed with water (3×100 mL), dried over MgSO4, and concentrated in vacuo. The residue was thrice dissolved in MeCN and concentrated in vacuo to afford a crude sample of 2-methoxymethoxy-4-methoxy-5-bromophenyl boronic acid as a light brown solid (343 mg): TLC (EtOAc) Rf=0.50, stained by KMnO4; 1H-NMR (400 MHz, CDCl3) δ 7.97 (s, 1H), 6.75 (s, 1H), 5.97 (s, 2H), 5.29 (s, 2H), 3.91 (s, 3H), 3.52 (s, 3H). To this crude boronic acid dissolved in benzene:DMSO (10:1) was added N-methyliminodiacetic acid (210 mg, 1.43 mmol). The flask was fitted with a Dean-Stark trap and a reflux condenser and the mixture was refluxed with stirring for 11 h followed by concentration in vacuo. The resulting crude product was adsorbed onto Florisil gel from a MeCN solution. The resulting powder was dry-loaded on top of a silica gel column slurry-packed with Et2O. The column was flushed with a copious volume of Et2O and then the product was eluted with Et2O:MeCN 1:1 to yield building block 14 as an off-white solid (365 mg, 68% yield over two steps).

1. customvial equipped with a stir bar
2. customThe vial was sealed with a septum
3. customcap
4. customremoved from the glove box
5. customadded DMSO (11 mL) and the resulting mixture was sealed under an atmosphere of argon
6. temperatureto cool to 23° C.
7. addition1 M aq. NaOH was added (0.9 mL, 0.9 mmol)
8. stirringThe mixture was stirred at 23° C. for 10 minutes
9. additiondiluted with saturated aq. NH4Cl (50 mL), water (50 mL), and Et2O (100 mL)
10. customThe layers were separated
11. washthe organic phase was washed with water (3×100 mL)
12. dry with materialdried over MgSO4
13. concentrationconcentrated in vacuo
14. dissolutiondissolved in MeCN
15. concentrationconcentrated in vacuo