4-Fluorobenzoyl chloride → 4-Fluorophenyl 2-[4-[2-(1-pyrrolidinyl)ethoxy]phenyl]benzo[b]thiophen-3-yl ketone

HRID 1387080Notes

Reaction equation

HRID 1387080 reaction equation
[S:1]1[C:5]([C:6]2[CH:19]=[CH:18][C:9]([O:10][CH2:11][CH2:12][N:13]3[CH2:17][CH2:16][CH2:15][CH2:14]3)=[CH:8][CH:7]=2)=[CH:4][C:3]2[CH:20]=[CH:21][CH:22]=[CH:23][C:2]1=2.[F:24][C:25]1[CH:33]=[CH:32][C:28]([C:29](Cl)=[O:30])=[CH:27][CH:26]=1.[Al].C(=O)(O)[O-].[Na+]>ClCCl.[Ti](Cl)(Cl)(Cl)Cl.O>[N:13]1([CH2:12][CH2:11][O:10][C:9]2[CH:18]=[CH:19][C:6]([C:5]3[S:1][C:2]4[CH:23]=[CH:22][CH:21]=[CH:20][C:3]=4[C:4]=3[C:29]([C:28]3[CH:32]=[CH:33][C:25]([F:24])=[CH:26][CH:27]=3)=[O:30])=[CH:7][CH:8]=2)[CH2:17][CH2:16][CH2:15][CH2:14]1

Participants

8

Reactant 4

HCID 678794-Fluorobenzoyl chlorideHCID 516892Sodium BicarbonateHCID 5359268AluminumHCID 106637082-[4-[2-(1-Pyrrolidinyl)ethoxy)phenyl]benzo[b]thiophene

Product 1

HCID 107182054-Fluorophenyl 2-[4-[2-(1-pyrrolidinyl)ethoxy]phenyl]benzo[b]thiophen-3-yl ketoneYield 90%

Reagents, catalysts & solvents 3

HCID 24193Titanium TetrachlorideCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

In a flame-dried, argon-filled flask were combined 1-[2-[4-(benzo[b]thiophen-2-yl)phenoxy]ethyl]pyrrolidine (Example 4, Part A) (3.54 g; 11.0 mmol) and 2.6 g (16.4 mmol) of 4-fluorobenzoyl chloride in 130 mL of dichloromethane. The mixture was cooled in an ice-water bath and protected from light with aluminum foil. Titanium tetrachloride (8.3 g; 43.8 mmol) was added dropwise. The mixture was stirred overnight while allowed to warm to room temperature. The mixture was poured into a rapidly stirred solution of 300 mL of saturated aqueous sodium bicarbonate. After stirring for 1 h, the mixture was transferred to a separatory funnel with 200 mL of water and extracted with dichloromethane (2×150 mL). The combined organics were dried by passage through sodium sulfate. The title compound was isolated as a yellow oil (4.4 g; 90% yield) by preparation HPLC using PrepLC, eluting with hexanes/THF/Et3N (75:20:5).

Workup

  1. additionIn a flame-dried, argon-filled flask
  2. temperatureThe mixture was cooled in an ice-water bath
  3. stirringAfter stirring for 1 h
  4. extractionextracted with dichloromethane (2×150 mL)
  5. dry with materialThe combined organics were dried by passage through sodium sulfate

Sources & evidence

ORD record
ord-17790654554f45ccacd9c6478f58e9e1
Source dataset
uspto-grants-2001_07
Patent number
US06265575B1

Reaction notes

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