3,4-Difluorobenzoyl chloride → 3,4-Difluorophenyl 2-[4-[2-(1-Pyrrolidinyl)ethoxy]phenyl]benzo[b]thiophen-3-yl Ketone

HRID 1387041Notes

Reaction equation

HRID 1387041 reaction equation
[N:1]1([CH2:6][CH2:7][O:8][C:9]2[CH:14]=[CH:13][C:12]([C:15]3[S:19][C:18]4[CH:20]=[CH:21][CH:22]=[CH:23][C:17]=4[CH:16]=3)=[CH:11][CH:10]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[F:24][C:25]1[CH:26]=[C:27]([CH:31]=[CH:32][C:33]=1[F:34])[C:28](Cl)=[O:29]>Cl[Ti](Cl)(Cl)Cl>[N:1]1([CH2:6][CH2:7][O:8][C:9]2[CH:14]=[CH:13][C:12]([C:15]3[S:19][C:18]4[CH:20]=[CH:21][CH:22]=[CH:23][C:17]=4[C:16]=3[C:28]([C:27]3[CH:31]=[CH:32][C:33]([F:34])=[C:25]([F:24])[CH:26]=3)=[O:29])=[CH:11][CH:10]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

4

Reactant 2

HCID 27245193,4-Difluorobenzoyl chlorideHCID 106637082-[4-[2-(1-Pyrrolidinyl)ethoxy)phenyl]benzo[b]thiophene

Product 1

HCID 211827863,4-Difluorophenyl 2-[4-[2-(1-Pyrrolidinyl)ethoxy]phenyl]benzo[b]thiophen-3-yl KetoneYield 37%

Reagents, catalysts & solvents 1

HCID 24193Titanium TetrachlorideCatalyst

Conditions

Temperature
0 °C

Procedure

A slurry of 3.23 g (10 mmol) of 2-[4-[2-(1-pyrrolidinyl)ethoxy)phenyl]benzo[b]thiophene in 50 mL of 1,2′dichloroethane was treated with 1.76 g (10 mmol) of 3,4-difluorobenzoyl chloride at 0° C. The mixture was protected from light and 4.4 mL (40 mmol) TiCl4 was added dropwise. The reaction was stirred at 0° C. for 5 h at which time it was quenched by carefully pouring it into 400 mL of saturated aqueous NaHCO3. To this was added EtOAc (200 mL), and the two layers were separated. The aqueous layer was extracted with EtOAc (2×50 mL). The combined organic layers were dried over Na2SO4 and evaporated in vacuo to give a crude oil which was purified by chromatography (SiO2; 2% MeOH in CHCl3) to afford 1.7 g (3.7 mmol; 37%) of the ketone as a viscous oil.

Workup

  1. additionwas added dropwise
  2. customwas quenched
  3. additionby carefully pouring it into 400 mL of saturated aqueous NaHCO3
  4. additionTo this was added EtOAc (200 mL)
  5. customthe two layers were separated
  6. extractionThe aqueous layer was extracted with EtOAc (2×50 mL)
  7. dry with materialThe combined organic layers were dried over Na2SO4
  8. customevaporated in vacuo
  9. customto give a crude oil which
  10. customwas purified by chromatography (SiO2; 2% MeOH in CHCl3)

Sources & evidence

ORD record
ord-874355640211463283c6df3784098cdc
Source dataset
uspto-grants-2001_07
Patent number
US06265575B1

Reaction notes

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