반응 #464587

반응 방정식

6-methoxy-2-[4-[2-(1-pyrrolidinyl)ethoxy]phenyl]benzo[b]thiophene

sodium bicarbonate

3-Bromo-4-fluorobenzoic acid

oxalyl chloride

calcium chloride

aluminum chloride

→

3-bromo-4-fluorophenyl 6-methoxy-2-[4-[2-(1-pyrrolidinyl)-ethoxy]phenyl]benzo[b]thiophen-3-yl ketone

용매

dichloromethane

반응 조건

후처리

1. 1
   workup.ADDITIONfilled
2. 2
   기타drying tube
3. 3
   농축The mixture was concentrated under reduced pressure to a white solid acid chloride
4. 4
   workup.DISSOLUTIONThe crude acid chloride was dissolved in 50 mL of dichloroethane in an argon atmosphere
5. 5
   workup.ADDITIONTo this was added at 0° C
6. 6
   workup.STIRRINGThe mixture was stirred in the cold for 4 h
7. 7
   workup.STIRRINGstirred for 1 h
8. 8
   추출Extraction
9. 9
   세척the combined organics were washed with brine
10. 10
    건조dried by passage through sodium sulfate
11. 11
    세척eluting with a gradient of EtOAc(100-90%)/Et3N(0-5%)/MeOH(0-5%)

실험 절차

3-Bromo-4-fluorobenzoic acid (0.66 g; 3.0 mmol) and 1.57 mL (18.0 mmol) of oxalyl chloride in 10 mL of dichloromethane in a flask protected from moisture by a calcium chloride filled drying tube was stirred at room temperature for 24 h. The mixture was concentrated under reduced pressure to a white solid acid chloride. The crude acid chloride was dissolved in 50 mL of dichloroethane in an argon atmosphere, To this was added at 0° C. 6-methoxy-2-[4-[2-(1-pyrrolidinyl)ethoxy]phenyl]benzo[b]thiophene (Example 1, Part B)(0.72 g; 2.0 mmol) and 1.6 g (12.0 mmol) of aluminum chloride. The mixture was stirred in the cold for 4 h, then poured into 200 mL of saturated aqueous sodium bicarbonate, and stirred for 1 h. Extraction was carried out with EtOAc (4×50 mL) and the combined organics were washed with brine and dried by passage through sodium sulfate. The mixture was subjected to flash chromatography on silica gel, eluting with a gradient of EtOAc(100-90%)/Et3N(0-5%)/MeOH(0-5%) to afford 3-bromo-4-fluorophenyl 6-methoxy-2-[4-[2-(1-pyrrolidinyl)-ethoxy]phenyl]benzo[b]thiophen-3-yl ketone contaminated with starting benzothiophene. This mixture was used without further purification.

출처