p-Toluenesulfonyl azide → 3-Amino-N-tert-butyl-5-chlorothiophene-2-sulfonamide

HRID 1419740Notes

Reaction equation

HRID 1419740 reaction equation
[C:1]([NH:5][S:6]([C:9]1[S:10][C:11]([Cl:14])=[CH:12][CH:13]=1)(=[O:8])=[O:7])([CH3:4])([CH3:3])[CH3:2].[Li]CCCC.C1(C)C=CC(S([N:29]=[N+]=[N-])(=O)=O)=CC=1.[BH4-].[Na+]>O1CCCC1.[Br-].C([P+](CCCC)(CCCC)CCCC)CCCCCCCCCCCCCCC.O>[C:1]([NH:5][S:6]([C:9]1[S:10][C:11]([Cl:14])=[CH:12][C:13]=1[NH2:29])(=[O:7])=[O:8])([CH3:4])([CH3:2])[CH3:3]

Participants

8

Reactant 4

HCID 13661p-Toluenesulfonyl azideHCID 4311764Sodium borohydrideHCID 101063235-Chlorothiophene-2-sulfonic acid tert-butylamideHCID 178418339Butyllithium

Product 1

HCID 109675263-Amino-N-tert-butyl-5-chlorothiophene-2-sulfonamideYield 100.7%

Reagents, catalysts & solvents 3

HCID 84716Hexadecyltributylphosphonium bromideCatalystHCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-20 °C

Procedure

A solution of 38.1 g (0.15 mol) of 5-chlorothiophene-2-sulfonic acid tert-butylamide in 300 ml of dry tetrahydrofuran was cooled to -70° C, and n-BuLi (190 ml, 1.6M in hexane) was added, maintaining the temperature <-65° C. After addition, the mixture was allowed to warm to -20° C. and stirred at this temperature for 30 min. A solution of p-toluenesulfonyl azide (34 g, 0.17 mol) in 100 ml of dry tetrahydrofuran was added, maintaining the temperature at -20° C., and the cooling bath was removed. After the mixture had reached room temperature, water (100 ml) was added. The organic phase was isolated and the aqueous phase was extracted with toluene (2×50 ml). To the combined organic phases was added hexadecyltributylphosphonium bromide (7.62 g, 15 mmol) followed by the dropwise addition of a solution of sodium borohydride (6.58 g, 0.174 mol) in 20 ml of water with stirring and cooling to room temperature. The mixture was stirred over night at room temperature, and water (100 ml) was added. The organic phase was isolated, washed with water (2×100 ml), dried, and evaporated to dryness. The oily residue was dissolved in ethyl acetate (150 ml) and washed with 1N sodium hydroxide (6×100 ml). The organic phase was dried with sodium sulfate, and evaporated to afford a quantitative yield (40.6 g) of crude title compound as an oil, which was used without further purification in the next step.

Workup

  1. temperaturemaintaining the temperature <-65° C
  2. additionAfter addition
  3. temperaturemaintaining the temperature at -20° C.
  4. customthe cooling bath was removed
  5. customhad reached room temperature
  6. additionwater (100 ml) was added
  7. customThe organic phase was isolated
  8. extractionthe aqueous phase was extracted with toluene (2×50 ml)
  9. stirringwith stirring
  10. temperaturecooling to room temperature
  11. stirringThe mixture was stirred over night at room temperature
  12. customThe organic phase was isolated
  13. washwashed with water (2×100 ml)
  14. customdried
  15. customevaporated to dryness
  16. dissolutionThe oily residue was dissolved in ethyl acetate (150 ml)
  17. washwashed with 1N sodium hydroxide (6×100 ml)
  18. dry with materialThe organic phase was dried with sodium sulfate
  19. customevaporated

Sources & evidence

ORD record
ord-46a390fa615a4a3bb1935f6e53d1e3bf
Source dataset
uspto-grants-1999_03
Patent number
US05889002

Reaction notes

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