Sulfuric Acid → (6-Bromo-benzo[b]thiophen-2-yl)-acetic acid methyl ester

HRID 250268Notes

Reaction equation

HRID 250268 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[CH:9]=[C:8]([CH2:10]C=O)[S:7][C:6]=2[CH:13]=1.[C:14](O)(C)(C)C.CC(=CC)C.Cl([O-])=O.[Na+].OP([O-])(O)=O.[Na+].S(=O)(=O)(O)O.[C:39]([O-:42])(O)=[O:40].[Na+]>O>[CH3:14][O:42][C:39](=[O:40])[CH2:10][C:8]1[S:7][C:6]2[CH:13]=[C:2]([Br:1])[CH:3]=[CH:4][C:5]=2[CH:9]=1

Participants

9

Reactant 7

HCID 1118Sulfuric AcidHCID 6386tert-ButanolHCID 105532-Methyl-2-buteneHCID 516892Sodium BicarbonateHCID 23668197Sodium ChloriteHCID 23672064Monosodium phosphateHCID 86625401HCID 86625401, compound

Product 1

HCID 67271604(6-Bromo-benzo[b]thiophen-2-yl)-acetic acid methyl esterYield 61%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Conditions

Temperature
0 °C

Procedure

To a 0° C. solution of (6-bromo-benzo[b]thiophen-2-yl)-acetaldehyde (2.21 g; 8.66 mmol) in t-butyl alcohol (50 mL; 526.36 mmoles; 50.00 mL; 39.015 g) and 2-methyl-2-butene (20 mL; 188 mmol) is added a solution of sodium chlorite (6.27 g; 69.3 mmol) in water (20 mL) and a solution of sodium phosphate monobasic (4.20 g; 34.6 mmol) in water (10 mL). The reaction mixture is stirred at 0° C. for 12 hours while warming to room temperature. The mixture is extracted with EtOAc (50 mL×2). The combined organic layers are dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude product is dissolved in methanol (30 mL). Sulfuric acid (1.0 mL; 18.8 mmol) is added and the mixture is stirred at 95° C. for 4 hours. The mixture is neutralized with aqueous NaHCO3 and concentrated under reduced pressure. The residual aqueous mixture is extracted with EtOAc (50 mL×2). The combined organic layers are dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude product is purified via flash chromatography eluting with 20% EtOAc/Hexanes. The appropriate fractions are combined and concentrated under reduced pressure to afford the title compound (1.51 g, 61%). ES/MS m/e (M+18):303.8; (M−1):284.7

Workup

  1. temperaturewhile warming to room temperature
  2. extractionThe mixture is extracted with EtOAc (50 mL×2)
  3. dry with materialThe combined organic layers are dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. dissolutionThe crude product is dissolved in methanol (30 mL)
  7. stirringthe mixture is stirred at 95° C. for 4 hours
  8. concentrationconcentrated under reduced pressure
  9. extractionThe residual aqueous mixture is extracted with EtOAc (50 mL×2)
  10. dry with materialThe combined organic layers are dried over Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated under reduced pressure
  13. customThe crude product is purified via flash chromatography
  14. washeluting with 20% EtOAc/Hexanes
  15. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-70013dfb896049a79698121c128cd0b2
Source dataset
uspto-grants-2011_01
Patent number
US07863302B2

Reaction notes

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