Hydrochloric Acid → 2-(3-Methoxy-propyl)-3-methyl-thiophene

HRID 252268Notes

Reaction equation

HRID 252268 reaction equation
[Mg].II.Br[C:5]1[S:6][CH:7]=[CH:8][C:9]=1[CH3:10].[CH3:11][O:12][CH2:13][CH2:14][CH2:15]OS(C1C=CC(C)=CC=1)(=O)=O.Cl>C(OCC)C.BrC1SC=CC=1C>[CH3:11][O:12][CH2:13][CH2:14][CH2:15][C:5]1[S:6][CH:7]=[CH:8][C:9]=1[CH3:10]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 807IodineHCID 843142-Bromo-3-methylthiopheneHCID 5462224MagnesiumHCID 135229883-Methoxypropyl 4-methylbenzenesulfonate

Product 1

HCID 668565572-(3-Methoxy-propyl)-3-methyl-thiophene

Reagents, catalysts & solvents 2

HCID 843142-Bromo-3-methylthiopheneCatalystHCID 3283Diethyl EtherSolvent3×

Conditions

Temperature
30 °C

Procedure

Magnesium turnings (365 mg, 15.0 mmol, 1.5 equiv.) were suspended in 15 ml dry diethyl ether. A crystal of iodine and a few drops of 2-bromo-3-methylthiophene in 10 ml ether were added till the reaction started (3 min. with heating to 30° C.). The remaining solution of 2-bromo-3-methylthiophene (total 2.44 g, 10.0 mmol, 1.0 equiv.) was added dropwise to maintain the reaction at reflux. The reaction mixture was refluxed for 30 min. Toluene-4-sulfonic acid 3-methoxy-propyl ester (2.13 g, 12.0 mmol, 1.2 equiv.) dissolved in 5 ml diethyl ether was added dropwise and the yellow solution was refluxed again for 2 hours. The brown suspension was cooled, acidified with 1N HCl and extracted twice with ethyl acetate. The combined organics were washed with KHSO4/K2SO4 and brine, dried over Na2SO4, filtered, evaporated and chromatographed on a 50 g Silicagel cartridge with heptane and than MTBE-heptane 1:9 as solvent to give 2-(3-methoxy-propyl)-3-methyl-thiophene, 410 mg, m/e 170.0 (MH+) by GC/MS.

Workup

  1. temperatureto maintain
  2. customthe reaction
  3. temperatureat reflux
  4. temperatureThe reaction mixture was refluxed for 30 min
  5. additionwas added dropwise
  6. temperaturethe yellow solution was refluxed again for 2 hours
  7. temperatureThe brown suspension was cooled
  8. extractionextracted twice with ethyl acetate
  9. washThe combined organics were washed with KHSO4/K2SO4 and brine
  10. dry with materialdried over Na2SO4
  11. filtrationfiltered
  12. customevaporated
  13. customchromatographed on a 50 g Silicagel cartridge with heptane and than MTBE-heptane 1:9 as solvent

Sources & evidence

ORD record
ord-ddb5c2e17f394f9c8d725315dd4ac8e4
Source dataset
uspto-grants-2011_01
Patent number
US07868030B2

Reaction notes

Loading…