Benzo(B)Thiophene → 5-Bromo2-methylphenyl benzo[b]thiophen-2-yl ketone

HRID 1514546Notes

Reaction equation

HRID 1514546 reaction equation
[CH:1]1[CH:2]=[CH:3][C:4]2[S:9][CH:8]=[CH:7][C:5]=2[CH:6]=1.C([Li])CCC.CON(C)[C:18](=[O:27])[C:19]1[CH:24]=[C:23]([Br:25])[CH:22]=[CH:21][C:20]=1[CH3:26].[Cl-].[NH4+]>C(OCC)C>[S:9]1[C:8]([C:18]([C:19]2[CH:24]=[C:23]([Br:25])[CH:22]=[CH:21][C:20]=2[CH3:26])=[O:27])=[CH:7][C:5]2[CH:6]=[CH:1][CH:2]=[CH:3][C:4]1=2

Participants

6

Reactant 4

HCID 7221Benzo(B)ThiopheneHCID 25517Ammonium ChlorideHCID 653071935-bromo-N-methoxy-N,2-dimethylbenzamideHCID 178418339Butyllithium

Product 1

HCID 666080305-Bromo2-methylphenyl benzo[b]thiophen-2-yl ketoneYield 74.2%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Conditions

Temperature
-78 °C

Procedure

A solution of thianaphthene (543 mg) in diethyl ether (20 ml) was cooled to 0° C. under argon atmosphere, and thereto was added dropwise n-butyl lithium (2.44 M hexane solution, 1.74 ml). The reaction mixture was stirred at the same temperature for 3 hours. The reaction mixture was added dropwise to a solution of N-methoxy-N-methyl-5-bromo-2-methylbenzamide (1.15 g) obtained in Reference Example 4-(2) in diethyl ether (10 ml) cooled to −78° C. The mixture was warmed to room temperature and stirred for one hour. Added thereto was a saturated aqueous ammonium chloride solution. The mixture was extracted with ethyl acetate, washed with brine, and dried over sodium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=100:0-95:5) to give 5-bromo2-methylphenyl benzo[b]thiophen-2-yl ketone (995 mg) as a pale yellow syrup. APCI-Mass m/Z 331/333 (M+H). (2) The above 5-bromo2-methylphenyl benzo[b]thiophen-2-yl ketone was treated in a manner similar to Reference Example 5-(2) to give 1-(benzo[b]thiophen-2-ylmethyl)-5-bromo-2-methylbenezene as colorless oil.

Workup

  1. temperatureThe mixture was warmed to room temperature
  2. stirringstirred for one hour
  3. additionAdded
  4. extractionThe mixture was extracted with ethyl acetate
  5. washwashed with brine
  6. dry with materialdried over sodium sulfate
  7. customThe solvent was evaporated under reduced pressure
  8. customThe residue was purified by silica gel column chromatography (hexane:ethyl acetate=100:0-95:5)

Sources & evidence

ORD record
ord-938168f76cae4cbab7160c3ea392aa83
Source dataset
uspto-grants-2012_07
Patent number
US08222219B2

Reaction notes

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