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

HRID 1070332

반응식

HRID 1070332 반응식
[Br:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[F:11])[C:5]([OH:7])=O.C(Cl)(=O)C(Cl)=O.[Cl-].[Ca+2].[Cl-].[CH3:21][O:22][C:23]1[CH:24]=[CH:25][C:26]2[CH:30]=[C:29]([C:31]3[CH:36]=[CH:35][C:34]([O:37][CH2:38][CH2:39][N:40]4[CH2:44][CH2:43][CH2:42][CH2:41]4)=[CH:33][CH:32]=3)[S:28][C:27]=2[CH:45]=1.[Cl-].[Al+3].[Cl-].[Cl-].C(=O)(O)[O-].[Na+]>ClCCl>[CH3:21][O:22][C:23]1[CH:24]=[CH:25][C:26]2[C:30]([C:5]([C:4]3[CH:8]=[CH:9][C:10]([F:11])=[C:2]([Br:1])[CH:3]=3)=[O:7])=[C:29]([C:31]3[CH:32]=[CH:33][C:34]([O:37][CH2:38][CH2:39][N:40]4[CH2:44][CH2:43][CH2:42][CH2:41]4)=[CH:35][CH:36]=3)[S:28][C:27]=2[CH:45]=1

참가 물질

8

반응물 6

HCID 65578Oxalyl chlorideHCID 705093-Bromo-4-fluorobenzoic acidHCID 516892Sodium BicarbonateHCID 5284359Calcium ChlorideHCID 6451240Aluminum(III) ChlorideHCID 106894206-Methoxy-2-[4-(2-(1-pyrrolidinyl)ethoxy)phenyl]benzo[b]thiophene

생성물 1

HCID 211829863-Bromo-4-fluorophenyl 6-methoxy-2-[4-[2-(1-pyrrolidinyl)ethoxy]phenyl]benzo[b]thiophen-3-yl ketone

시약·촉매·용매 1

HCID 6344Dichloromethane용매

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.

후처리

  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%)

출처 및 근거

ORD 기록
ord-2534b3b4d11943df9ea48c79cca83d17
출처 데이터셋
uspto-grants-2001_06
특허 번호
US06251921B1

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