Methyl iodide → HCID 19759891, compound

HRID 1586868Notes

Reaction equation

HRID 1586868 reaction equation
[H-].[Na+].[CH3:3]I.[S:5]1(=[O:17])(=[O:16])[C:9]2[S:10][CH:11]=[CH:12][C:8]=2[CH2:7][CH:6]1[C:13]([OH:15])=[O:14]>CN(C=O)C>[CH3:3][C:6]1([C:13]([OH:15])=[O:14])[S:5](=[O:17])(=[O:16])[C:9]2[S:10][CH:11]=[CH:12][C:8]=2[CH2:7]1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 19759880HCID 19759880, compound

Product 1

HCID 19759891HCID 19759891, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

A suspension of sodium hydride (12.3 g, 60% dispersion in oil) in DMF (200 mL, distilled from calcium hydride) was cooled with stirring to 0° C. under a nitrogen atmosphere. Methyl iodide (18.5 mL, 0.29 mol) was added followed by the dropwise addition of 2,3-dihydrothieno[2,3-b]thiophene-2-carboxylic acid-1,1-dioxide (21.33 g. 0.0978 mol) in DMF (200 mL) over a period 1.25 hours. The reaction was stirred at 0° C. for an additional 2.25 hours, then quenched with water (100 mL) and 40% sodium hydroxide (2 mL). The basic solution was stirred for an additional 1 hour at 0° C., until hydrolysis of the ester was complete by tlc. 10% HCl was added to adjust the pH to 6, and the DMF removed in vacuo. The residue was partitioned between ethyl acetate and water. The pH of the aqueous phase was adjusted to 0 with 10% HCl, and the cloudy solution extracted with ethyl acetate (3×500 mL). The volume of ethyl acetate was reduced to 500 mL and extracted with 10% sodium hydroxide (3×300 mL). The aqueous phase was made acidic with concentrated HCl and extracted with two 400 mL portions of ethyl acetate. The combined organic extracts were washed with saturated brine, dried over magnesium sulfate, and filtered. The solvent was removed in vacuo to give an oil which solidified. The solid was triturated with cold methylene chloride (50 mL), filtered and dried in vacuo (0.5 mm, 40° C.) to give the title compound as a light tan powder.

Workup

  1. temperaturewas cooled
  2. stirringThe reaction was stirred at 0° C. for an additional 2.25 hours
  3. customquenched with water (100 mL) and 40% sodium hydroxide (2 mL)
  4. stirringThe basic solution was stirred for an additional 1 hour at 0° C., until hydrolysis of the ester
  5. addition10% HCl was added
  6. customthe DMF removed in vacuo
  7. customThe residue was partitioned between ethyl acetate and water
  8. extractionthe cloudy solution extracted with ethyl acetate (3×500 mL)
  9. extractionextracted with 10% sodium hydroxide (3×300 mL)
  10. extractionextracted with two 400 mL portions of ethyl acetate
  11. washThe combined organic extracts were washed with saturated brine
  12. dry with materialdried over magnesium sulfate
  13. filtrationfiltered
  14. customThe solvent was removed in vacuo
  15. customto give an oil which
  16. customThe solid was triturated with cold methylene chloride (50 mL)
  17. filtrationfiltered
  18. customdried in vacuo (0.5 mm, 40° C.)

Sources & evidence

ORD record
ord-e260c17a706a4fcab9a26a3afc580231
Source dataset
uspto-grants-1993_06
Patent number
US05216020

Reaction notes

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