Benzo(B)Thiophene → 1-Benzothien-2-yl(5-bromo-2-chlorophenyl)methanol

HRID 501903Notes

Reaction equation

HRID 501903 reaction equation
[S:1]1[CH:5]=[CH:4][C:3]2[CH:6]=[CH:7][CH:8]=[CH:9][C:2]1=2.C([Li])CCC.ClC1C=[CH:18][C:19]([Br:24])=[C:20](C=1)C=O.[Cl-:25].[NH4+].[O:27]1[CH2:31][CH2:30][CH2:29][CH2:28]1>O.C(OCC)(=O)C.CCCCCC>[S:1]1[C:2]2[CH:9]=[CH:8][CH:7]=[CH:6][C:3]=2[CH:4]=[C:5]1[CH:31]([C:30]1[CH:20]=[C:19]([Br:24])[CH:18]=[CH:28][C:29]=1[Cl:25])[OH:27]

Participants

9

Reactant 5

HCID 7221Benzo(B)ThiopheneHCID 8028Tetrahydrofuran2×HCID 25517Ammonium ChlorideHCID 153912792-Bromo-5-chlorobenzaldehydeHCID 178418339Butyllithium

Product 1

HCID 231033831-Benzothien-2-yl(5-bromo-2-chlorophenyl)methanol

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-78 °C

Procedure

Benzo[b]thiophene (1.12 g) was dissolved in tetrahydrofuran (50 ml). This solution was cooled to −78° C., and a solution of 1.58 M hexane (10.5 ml) of n-butyllithium was added dropwise to the solution, and the mixture was stirred for 15 minutes at −78° C. Then, 5-chloro-2-bromobenzaldehyde (3.15 g) dissolved in tetrahydrofuran (50 ml) was added dropwise to the reaction mixture, and the mixture was stirred for two hours at room temperature. Aqueous solution of saturated ammonium chloride was added to the reaction mixture, and then the solvent was evaporated from the filtrate under reduced pressure to give the residue. Ethyl acetate and water were added to the residue obtained, and extracted with ethyl acetate. The organic layer was dried over magnesium sulfate, the solvent was evaporated from the filtrate under reduced pressure to give the residue, and the residue was purified by silica gel column chromatography (n-hexane-ethyl acetate) to obtain 1-benzothien-2-yl(5-bromo-2-chlorophenyl)methanol (4.75 g). Imidazole (1.08 g) and tert-butyl dimethylchlorosilane (2.99 g) were added to a solution of 1-benzothien-2-yl(5-bromo-2-chlorophenyl)methanol in dimethylformamide (100 ml), and the mixture was stirred for three hours at 70° C. Water was added to the reaction mixture, and extracted with diethyl ether. The organic layer was dried over magnesium sulfate, the solvent was evaporated therefrom under reduced pressure to give the residue, and the resulting residue was purified by silica gel column chromatography (n-hexane-ethyl acetate) to obtain [1-benzothien-2-yl(5-bromo-2-chloro phenyl)methoxy](tert-butyl) dimethylsilane (3.34 g).

Workup

  1. additionwas added dropwise to the reaction mixture
  2. stirringthe mixture was stirred for two hours at room temperature
  3. customthe solvent was evaporated from the filtrate under reduced pressure
  4. customto give the residue
  5. customobtained
  6. extractionextracted with ethyl acetate
  7. dry with materialThe organic layer was dried over magnesium sulfate
  8. customthe solvent was evaporated from the filtrate under reduced pressure
  9. customto give the residue
  10. customthe residue was purified by silica gel column chromatography (n-hexane-ethyl acetate)

Sources & evidence

ORD record
ord-d9d97c5642e6426a815612767e4b408e
Source dataset
uspto-grants-2010_08
Patent number
US07772407B2

Reaction notes

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