Reaktion #165841

Reaktionsgleichung

tert-butyl N-[5-bromo-3-(2-trimethylsilylethynyl)pyrazin-2-yl]-N-tert-butoxycarbonyl-carbamate

(4-isopropylsulfonylphenyl)boronic acid

sodium metabisulphite

K3PO4

→

product

tert-butyl N-(3-ethynyl-5-(4-(isopropylsulfonyl)phenyl)pyrazin-2-yl)N-tert-butoxycarbonyl-carbamate

Lösungsmittel

MeCN

water

ethyl acetate

water

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGshaken well
2. 2
   Sonstigethe layer separated
3. 3
   TrocknenThe organic fraction was dried over MgSO4
4. 4
   Filtrationfiltered
5. 5
   workup.ADDITIONthe filtrate was treated with 3-mercaptopropyl ethyl sulphide on silica (0.8 mmol/g)(1 g)
6. 6
   Sonstigepre-absorbed onto silica gel
7. 7
   Sonstigethen purified by column chromatography on silica gel eluting with 30-40% EtOAc/petroleu ether
8. 8
   Einengenconcentrated in vacuo

Vorschrift

tert-butyl N-[5-bromo-3-(2-trimethylsilylethynyl)pyrazin-2-yl]-N-tert-butoxycarbonyl-carbamate (3 g, 6.377 mmol) and (4-isopropylsulfonylphenyl)boronic acid (1.491 g, 6.536 mmol) were dissolved in MeCN (60.00 mL) then treated with water (12.00 mL) and K3PO4 (2.706 g, 12.75 mmol) then degassed/flushed nitrogen (×5 cycles). Treated with Pd[P(tBu)3]2 (162.9 mg, 0.3188 mmol) and reflushed Vac/Nitrogen ×5. The resulting mixture was stirred at room temperature for 1 h. The reaction mixture was poured quickly into a mixture of ethyl acetate (500 mL), water (90 mL) and 1% aqueous sodium metabisulphite at 4° C., shaken well and the layer separated. The organic fraction was dried over MgSO4, filtered and the filtrate was treated with 3-mercaptopropyl ethyl sulphide on silica (0.8 mmol/g)(1 g), pre-absorbed onto silica gel then purified by column chromatography on silica gel eluting with 30-40% EtOAc/petroleu ether. Product fractions were combined and concentrated in vacuo to leave the product as a yellow/ brown viscous oil. Triturated with petroleum ether and some diethyl ether and a small amount of dichloromethane added. Left to stand at room temperature for 30 min and beige crystals formed, isolated by filtration to leave the product as a beige solid (1.95 g, 61%); 1H NMR (400 MHz, DMSO) d 1.20 (m, 6H), 1.39 (s, 18H), 3.50 (m, 1H), 5.01 (s, 1H), 8.03 (m, 2H), 8.46 (m, 2H) and 9.37 (s, 1H) ppm.

Quelle