4-Iodobenzoic acid → 4-Iodophenyl 2-[4-[2-(1-Pyrrolidinyl)ethoxy]phenyl]benzo[b]thiophen-3-yl Ketone

HRID 1387060Notes

Reaction equation

HRID 1387060 reaction equation
[I:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][CH:3]=1.O=S(Cl)Cl.[N:15]1([CH2:20][CH2:21][O:22][C:23]2[CH:28]=[CH:27][C:26]([C:29]3[S:33][C:32]4[CH:34]=[CH:35][CH:36]=[CH:37][C:31]=4[CH:30]=3)=[CH:25][CH:24]=2)[CH2:19][CH2:18][CH2:17][CH2:16]1.C([O-])(O)=O.[Na+]>ClCCCl.CN(C=O)C.Cl[Ti](Cl)(Cl)Cl>[N:15]1([CH2:20][CH2:21][O:22][C:23]2[CH:28]=[CH:27][C:26]([C:29]3[S:33][C:32]4[CH:34]=[CH:35][CH:36]=[CH:37][C:31]=4[C:30]=3[C:6]([C:5]3[CH:4]=[CH:3][C:2]([I:1])=[CH:10][CH:9]=3)=[O:8])=[CH:25][CH:24]=2)[CH2:19][CH2:18][CH2:17][CH2:16]1

Participants

8

Reactant 4

HCID 120854-Iodobenzoic acidHCID 24386Thionyl ChlorideHCID 516892Sodium BicarbonateHCID 106637082-[4-[2-(1-Pyrrolidinyl)ethoxy)phenyl]benzo[b]thiophene

Product 1

HCID 211826284-Iodophenyl 2-[4-[2-(1-Pyrrolidinyl)ethoxy]phenyl]benzo[b]thiophen-3-yl Ketone

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 24193Titanium TetrachlorideCatalystHCID 111,2-DichloroethaneSolvent

Conditions

Temperature
0 °C

Procedure

A slurry of 4-iodobenzoic acid (7.67 g, 30.9 mmol) in 300 mL of 1,2-dichloroethane and 2 drops of DMF was treated with SOCl2 (11.3 mL, 154.6 mmol). The resulting mixture was heated at reflux overnight. The clear solution was evaporated in vacuo, then the solid residue was resuspended in 1,2-dichloroethane and reconcentrated. The crude acid chloride was dissolved in 300 mL of 1,2-dichloroethane, and 2-[4-[2-(1-pyrrolidinyl)ethoxy]phenyl]benzo[b]thiophene (5.0 g, 15.5 mmol) was added. The solution was cooled to 0° C. and treated with TiCl4 (8.5 mL, 77.3 mmol). After 5.5 h, the reaction mixture was carefully poured into 600 mL of saturated aqueous NaHCO3. The layers were separated, and the aqueous phase was extracted with CHCl3 (3×300 mL). The combined organic phases were dried over Na2SO4, filtered, and concentrated in vacuo. Purification by PrepLC (SiO2; 1% MeOH in CHCl3, saturated with NH4OH) afforded 6.79 g (12.3 mmol; 79%) of the title product as a yellow foam.

Workup

  1. temperatureThe resulting mixture was heated
  2. temperatureat reflux overnight
  3. customThe clear solution was evaporated in vacuo
  4. dissolutionThe crude acid chloride was dissolved in 300 mL of 1,2-dichloroethane
  5. customThe layers were separated
  6. extractionthe aqueous phase was extracted with CHCl3 (3×300 mL)
  7. dry with materialThe combined organic phases were dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customPurification by PrepLC (SiO2; 1% MeOH in CHCl3, saturated with NH4OH)

Sources & evidence

ORD record
ord-351839297cd5403185c06292856f3e72
Source dataset
uspto-grants-2001_07
Patent number
US06265575B1

Reaction notes

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