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

HRID 1012028Notes

Reaction equation

HRID 1012028 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-5ea223a75fc648dea0f8284e890e7467
Source dataset
uspto-grants-2011_07
Patent number
US07977466B2

Reaction notes

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