Ethanethiol → {2-(4-Fluoro-phenyl)-6-hydroxy-benzo[b]thiophen-3-yl]-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-methanone

HRID 354078Notes

Reaction equation

HRID 354078 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:12][C:11]3[CH:13]=[C:14]([O:17]C)[CH:15]=[CH:16][C:10]=3[CH:9]=2)=[CH:4][CH:3]=1.[N:19]1([CH2:25][CH2:26][O:27][C:28]2[CH:36]=[CH:35][C:31]([C:32](Cl)=[O:33])=[CH:30][CH:29]=2)[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]1.[Cl-].[Cl-].[Cl-].[Al+3].C(S)C>ClCCCl>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:12][C:11]3[CH:13]=[C:14]([OH:17])[CH:15]=[CH:16][C:10]=3[C:9]=2[C:32]([C:31]2[CH:35]=[CH:36][C:28]([O:27][CH2:26][CH2:25][N:19]3[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]3)=[CH:29][CH:30]=2)=[O:33])=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 6343EthanethiolHCID 6451240Aluminum(III) ChlorideHCID 111190664-(2-(Piperidin-1-yl)ethoxy)benzoyl chlorideHCID 235129082-(4-Fluorophenyl)-6-methoxybenzo[b]thiophene

Product 1

HCID 10790742{2-(4-Fluoro-phenyl)-6-hydroxy-benzo[b]thiophen-3-yl]-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-methanone

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a solution of the product from Example 17, Step 1 (83 mg, 0.32 mmol) and 4-(2-Piperidin-1-yl-ethoxy)-benzoyl chloride (1.39 mL, 0.39 mmol) in 3.3 mL of 1,2-dichloroethane was added, in two portions, aluminum trichloride (322 mg, 2.4 mmol) and the reaction was heated at reflux for 1 hr. At this time the coupling was complete and demethylation was carried out cooling the reaction to room temperature, adding ethanethiol (0.10 mL, 1.41 mmol) dropwise and stirring at room temperature for a further 1.5 hrs. The reaction was quenched with saturated sodium bicarbonate solution and extracted twice with methylene chloride. The organic layers were combined, dried over anhydrous sodium sulfate, filtered, and concentrated. The crude material was chromatographed on silica gel using 1% MeOH:methylene chloride to 3% MeOH:methylene chloride as the gradient eluant to yield the title compound.

Workup

  1. temperaturethe reaction was heated
  2. temperatureat reflux for 1 hr
  3. temperaturedemethylation was carried out cooling
  4. customthe reaction to room temperature
  5. customThe reaction was quenched with saturated sodium bicarbonate solution
  6. extractionextracted twice with methylene chloride
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude material was chromatographed on silica gel using 1% MeOH

Sources & evidence

ORD record
ord-b049ac8fb3f346de894fd24e110d0e76
Source dataset
uspto-grants-2004_06
Patent number
US06756388B1

Reaction notes

Loading…