1,2-Dibromoethane → HCID 10651810, Verbindung

Temperatur

-78 °C

A −78° C. solution of 5-bromopyrid-2-yl 2-(1-pyrrolidinyl)ethyl ether (3.25 g, 12.0 mmol) in 40 mL of anhydrous THF was treated with n-BuLi (8.1 mL, 13.0 mmol, 1.6 M in hexanes). After 1 h, a slurry of MgBr2 [freshly prepared from Mg (365 mg, 15.0 mmol) and 1.3 mL of 1,2-dibromoethane] in 20 mL of anhydrous THF was added. The reaction mixture was stirred at −78° C. for an additional 10 min, and then the cold bath was removed. After 45 min, the Grignard reagent was added dropwise via a cannula to a solution of 6-benzyloxy-2-(dimethylamino)benzo[b]thiophen-3-yl 3-methoxy-4-[(1-pyrrolidinyl)methyl]phenyl ketone (5 g, 10.0 mmol) in 50 mL of THF at 0° C. The resulting mixture was stirred for 2 h at 0° C. and then was allowed to warm to ambient temperature. After 5 h, the reaction mixture was poured into 200 mL of saturated aqueous NH4Cl. The layers were separated, and the aqueous phase was extracted with CHCl3 (3×50 mL). The combined organic phases were dried over Na2SO4, filtered, and concentrated in vacuo. Purification by PrepLC (SiO2; gradient of 85:10:5 hexanes-THF-TEA to 75:20:5 hexanes-THF-TEA) afforded 2.9 g (4.48 mmol; 45%) of the title product as a viscous orange oil.

1. additionwas added
2. customthe cold bath was removed
3. waitAfter 45 min
4. stirringThe resulting mixture was stirred for 2 h at 0° C.
5. temperatureto warm to ambient temperature
6. waitAfter 5 h
7. customThe layers were separated
8. extractionthe aqueous phase was extracted with CHCl3 (3×50 mL)
9. dry with materialThe combined organic phases were dried over Na2SO4
10. filtrationfiltered
11. concentrationconcentrated in vacuo
12. customPurification by PrepLC (SiO2; gradient of 85:10:5 hexanes-THF-TEA to 75:20:5 hexanes-THF-TEA)

ORD-Eintrag

ord-9200e7b1f69b476486fb3b095543590e

Quelldatensatz

uspto-grants-2001_07

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US06265575B1