1,3-Dibromobenzene → 3-Bromophenyl 6-fluorobenzo[b]thiophen-2-yl ketone

HRID 1625797Notes

Reaction equation

HRID 1625797 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Br:8])[CH:3]=1.C([Li])CCC.[F:14][C:15]1[CH:16]=[CH:17][C:18]2[CH:22]=[C:21]([C:23](=[O:28])N(OC)C)[S:20][C:19]=2[CH:29]=1.[Cl-].[NH4+]>O1CCCC1>[F:14][C:15]1[CH:16]=[CH:17][C:18]2[CH:22]=[C:21]([C:23]([C:2]3[CH:7]=[CH:6][CH:5]=[C:4]([Br:8])[CH:3]=3)=[O:28])[S:20][C:19]=2[CH:29]=1

Participants

6

Reactant 4

HCID 79271,3-DibromobenzeneHCID 25517Ammonium ChlorideHCID 860283256-fluoro-2-(N-methoxy-N-methylcarbamoyl)benzo[b]thiopheneHCID 178418339Butyllithium

Product 1

HCID 666087883-Bromophenyl 6-fluorobenzo[b]thiophen-2-yl ketoneYield 68.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 1,3-dibromobenzene (493 mg) in tetrahydrofuran (10 ml) was cooled to −78° C. under argon atmosphere, and thereto was added dropwise n-butyl lithium (2.44 M hexane solution, 0.86 ml). The reaction mixture was stirred at the same temperature for 30 minutes, and thereto was added dropwise a solution of the above 6-fluoro-2-(N-methoxy-N-methylcarbamoyl)benzo[b]thiophene (500 mg) in tetrahydrofuran (3 ml). The mixture was warmed to room temperature, and added thereto was a saturated aqueous ammonium chloride solution. The mixture was extracted with ethyl acetate, and dried over magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=95:5-85:15) to give 3-bromophenyl 6-fluorobenzo[b]thiophen-2-yl ketone (479 mg) as a pale yellow solid. APCI-Mass m/Z 335/337 (M+NH4).

Workup

  1. additionadded
  2. extractionThe mixture was extracted with ethyl acetate
  3. dry with materialdried over magnesium sulfate
  4. customThe solvent was evaporated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (hexane:ethyl acetate=95:5-85:15)

Sources & evidence

ORD record
ord-2829356ee04249cc8d0e5b922f5d1cbd
Source dataset
uspto-grants-2014_07
Patent number
US08785403B2

Reaction notes

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