Methanesulfonyl chloride → Tert-butyl 5-(methylsulfonamido)thiophene-2-carboxylate

HRID 59748Notes

Reaction equation

HRID 59748 reaction equation
NC1SC(C(OC(C)(C)C)=O)=CC=1.CS(Cl)(=O)=O.[CH3:19][S:20]([N:23]([C:28]1[S:32][C:31]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])=[CH:30][CH:29]=1)S(C)(=O)=O)(=[O:22])=[O:21]>N1C=CC=CC=1>[CH3:19][S:20]([NH:23][C:28]1[S:32][C:31]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])=[CH:30][CH:29]=1)(=[O:21])=[O:22]

Participants

5

Reactant 3

HCID 31297Methanesulfonyl chlorideHCID 86703850Tert-butyl 5-aminothiophene-2-carboxylateHCID 86703852tert-butyl 5-(N-(methylsulfonyl)-methylsulfonamido)thiophene-2-carboxylate

Product 1

HCID 86703851Tert-butyl 5-(methylsulfonamido)thiophene-2-carboxylate

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

To a solution of tert-butyl 5-aminothiophene-2-carboxylate (Int. 55) (1.481 g, 7.43 mmol) in pyridine (50 ml) cooled to 0° C., methanesulfonyl chloride (0.695 ml, 8.92 mmol) was added drop-wise. The reaction was warmed to RT and stirred for 3 days. The solvent was removed under vacuum, and the residue was portioned between EtOAc and 1N HCl; the organic phase was washed with brine, dried over sodium sulfate, filtered and evaporated to dryness. The crude was purified by flash chromatography on silica gel cartridge (petroleum ether/EtOAc=8/2) to afford tert-butyl 5-(methylsulfonamido)-thiophene-2-carboxylate (Int. 56) (773 mg, 2.79 mmol, MS/ESI+299.9 [MNa]+) and tert-butyl 5-(N-(methylsulfonyl)-methylsulfonamido)thiophene-2-carboxylate (Int. 57) (420 mg, 1.182 mmol, MS/ESI+ not detectable [MH]+).

Workup

  1. customThe solvent was removed under vacuum
  2. washthe organic phase was washed with brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. customevaporated to dryness
  6. customThe crude was purified by flash chromatography on silica gel cartridge (petroleum ether/EtOAc=8/2)

Sources & evidence

ORD record
ord-81592831319546c0b88547d4365b86a8
Source dataset
uspto-grants-2016_09
Patent number
US09440954B2

Reaction notes

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