1,2-Dichloroethane → 1-[2-[4-[3-[4-[3-(1-Pyrrolidinyl)-1-propynyl]benzyl]benzo[b]thiophen-2-yl]phenoxy]ethyl]pyrrolidine Dioxalate

温度

0 °C

A slurry of 4-iodobenzoic acid (7.67 g, 30.9 mmol) in 300 mL of 1,2-dichloroethane and 2 drops of DMF was treated with SOCl2 (11.3 mL, 154.6 mmol). The resulting mixture was heated at reflux overnight. The clear solution was evaporated in vacuo, then the solid residue was resuspended in 1,2-dichloroethane and reconcentrated. The crude acid chloride was dissolved in 300 mL of 1,2-dichloroethane, and 2-[4-[2-(1-pyrrolidinyl)ethoxy]phenyl]benzo[b]thiophene (5.0 g, 15.5 mmol) was added. The solution was cooled to 0° C. and treated with TiCl4 (8.5 mL, 77.3 mmol). After 5.5 h, the reaction mixture was carefully poured into 600 mL of saturated aqueous NaHCO3. The layers were separated, and the aqueous phase was extracted with CHCl3 (3×300 mL). The combined organic phases were dried over Na2SO4, filtered, and concentrated in vacuo. Purification by PrepLC (SiO2; 1% MeOH in CHCl3, saturated with NH4OH) afforded 6.79 g (12.3 mmol; 79%) of the title product as a yellow foam.

1. temperatureThe resulting mixture was heated
2. temperatureat reflux overnight
3. customThe clear solution was evaporated in vacuo
4. dissolutionThe crude acid chloride was dissolved in 300 mL of 1,2-dichloroethane
5. customThe layers were separated
6. extractionthe aqueous phase was extracted with CHCl3 (3×300 mL)
7. dry with materialThe combined organic phases were dried over Na2SO4
8. filtrationfiltered
9. concentrationconcentrated in vacuo
10. customPurification by PrepLC (SiO2; 1% MeOH in CHCl3, saturated with NH4OH)

ORDレコード

ord-df12d04c6d9d433fa81cefbe55af98b8

出典データセット

uspto-grants-2001_06

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US06251921B1