4-Fluorobenzoyl chloride → [2-(2-Dimethylamino-ethyl)-benzo[b]thiophen-3-yl]-(4-fluoro-phenyl)-methanone

HRID 746603Notes

Reaction equation

HRID 746603 reaction equation
[S:1]1[C:5]([CH2:6][CH2:7][N:8]([CH3:10])[CH3:9])=[CH:4][C:3]2[CH:11]=[CH:12][CH:13]=[CH:14][C:2]1=2.[F:15][C:16]1[CH:24]=[CH:23][C:19]([C:20](Cl)=[O:21])=[CH:18][CH:17]=1.[Cl-].[Al+3].[Cl-].[Cl-]>ClC(Cl)C>[CH3:9][N:8]([CH3:10])[CH2:7][CH2:6][C:5]1[S:1][C:2]2[CH:14]=[CH:13][CH:12]=[CH:11][C:3]=2[C:4]=1[C:20]([C:19]1[CH:23]=[CH:24][C:16]([F:15])=[CH:17][CH:18]=1)=[O:21]

Participants

5

Reactant 3

HCID 678794-Fluorobenzoyl chlorideHCID 6451240Aluminum(III) ChlorideHCID 58591561HCID 58591561, compound2×

Product 1

HCID 11674280[2-(2-Dimethylamino-ethyl)-benzo[b]thiophen-3-yl]-(4-fluoro-phenyl)-methanoneYield 47%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Procedure

To a solution of (2-Benzo[b]thiophen-2-yl-ethyl)-dimethylamine (Compound 1a, 1.1 mmol) in dichloroethane (1 mL) under N2 at 0° C., p-fluorobenzoyl chloride (1.32 mmol) and aluminum chloride (3.3 mmol, 1M in nitrobenzene) were added. The mixture was warmed to RT and stirred for 5 hrs, quenched in sat. NaHCO3 and extracted with EtOAc (4×). The combined organic layers were washed with brine, dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by silica gel column chromatography in EtOAc with gradient to EtOAc:methanol (99:1) as required. Compound 3-1, [2-(2-Dimethylamino-ethyl)-benzo[b]thiophen-3-yl]-(4-fluoro-phenyl)-methanone, was isolated in 47% yield (170 mg); MS (MH+)=327.8.

Workup

  1. customquenched in sat. NaHCO3
  2. extractionextracted with EtOAc (4×)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by silica gel column chromatography in EtOAc with gradient to EtOAc:methanol (99:1)

Sources & evidence

ORD record
ord-65d7715e11454e41adc82751603e6a00
Source dataset
uspto-grants-2008_07
Patent number
US07393865B2

Reaction notes

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