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

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.

1. additionfilled
2. customdrying tube
3. concentrationThe mixture was concentrated under reduced pressure to a white solid acid chloride
4. dissolutionThe crude acid chloride was dissolved in 50 mL of dichloroethane in an argon atmosphere
5. additionTo this was added at 0° C
6. stirringThe mixture was stirred in the cold for 4 h
7. stirringstirred for 1 h
8. extractionExtraction
9. washthe combined organics were washed with brine
10. dry with materialdried by passage through sodium sulfate
11. washeluting with a gradient of EtOAc(100-90%)/Et3N(0-5%)/MeOH(0-5%)

ORDレコード

ord-72f93e47c7554bb3903e89ae59c1ec7f

出典データセット

uspto-grants-2000_02

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US06025382