Sulfuric Acid → 3-(Toluene-2-sulfonylamino)-thiophene-2-carboxylic acid tert-butyl ester

HRID 2193898Notes

Reaction equation

HRID 2193898 reaction equation
[C:1]1([CH3:19])[C:2]([S:7]([NH:10][C:11]2[CH:15]=[CH:14][S:13][C:12]=2[C:16]([OH:18])=[O:17])(=[O:9])=[O:8])=[CH:3][CH:4]=[CH:5][CH:6]=1.OS(O)(=O)=O>>[C:1]([O:17][C:16]([C:12]1[S:13][CH:14]=[CH:15][C:11]=1[NH:10][S:7]([C:2]1[C:1]([CH3:19])=[CH:6][CH:5]=[CH:4][CH:3]=1)(=[O:9])=[O:8])=[O:18])([CH3:19])([CH3:2])[CH3:6]

Participants

3

Reactant 2

HCID 1118Sulfuric AcidHCID 224961893-(Toluene-2-sulfonylamino)-thiophene-2-carboxylic acid

Product 1

HCID 207757763-(Toluene-2-sulfonylamino)-thiophene-2-carboxylic acid tert-butyl esterYield 146.8%

Procedure

To a cold (−40° C.) mixture of 3-(Toluene-2-sulfonylamino)-thiophene-2-carboxylic acid (1.5 g, 5.05 mmol) in 1,4-dioxane/CHCl, (1:2, 12 mL) was bubbled 2-methyl-2-propene gas (15 mL) in a sealed tube. To this was added Conc. H2SO4 (0.070 mL, 1.3 mmol) and slowly warmed up to room temperature. The resultant reaction mixture was heated at 70° C. for 2.5 days in a sealed tube, cooled to −40° C., stopper was removed. The reaction mixture was slowly brought up to room temperature and stirred until the excess gas is released. The mixture was extracted with EtOAc, washed with aq. NaHCO3 solution, brine and dried. Evaporation of the solvent and purification of the residue on silica gel using EtOAc/hexane (1:10) as an eluent furnished 3-(Toluene-2-sulfonylamino)-thiophene-2-carboxylic acid tert-butyl ester (1.31 g, 73.5% based on 90% conversion). 1H NMR (CDCl3, 300 MHz) 9.89 (s, 1H), 8.01 (d, J=7.9 Hz, 1H), 7.43 (dt, J=7.5 Hz, 1.5 Hz, 1H), 7.3-7.25 (m, 3H), 7.2 (d, J=5.4 Hz, 1H), 2.69 (s, 3H), 1.56 (s, 9H).

Workup

  1. customwas bubbled 2-methyl-2-propene gas (15 mL) in a sealed tube
  2. customThe resultant reaction mixture
  3. temperaturewas heated at 70° C. for 2.5 days in a sealed tube
  4. temperaturecooled to −40° C.
  5. customstopper was removed
  6. customwas slowly brought up to room temperature
  7. extractionThe mixture was extracted with EtOAc
  8. washwashed with aq. NaHCO3 solution, brine
  9. customdried
  10. customEvaporation of the solvent and purification of the residue on silica gel

Sources & evidence

ORD record
ord-965328ee2039420cb75ef1c503bdaec4
Source dataset
uspto-grants-2012_12
Patent number
US08329924B2

Reaction notes

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