4-Chlorobenzenesulfonyl chloride → 3-[[(1,1-Dimethylethoxy)carbonyl]amino]propyl 4-chlorobenzenesulfonate

HRID 2078430Notes

Reaction equation

HRID 2078430 reaction equation
CC[CH2:3][CH:4]([CH3:6])[CH3:5].[Mn]([O-])(=O)(=O)=[O:8].[K+].C(N([CH2:18][CH3:19])CC)C.Cl.C[N:22]([CH3:24])C.[Cl:25][C:26]1[CH:31]=[CH:30][C:29]([S:32](Cl)(=[O:34])=[O:33])=[CH:28][CH:27]=1.[C:36]([O:39]CC)(=[O:38])C>C(Cl)Cl.O>[Cl:25][C:26]1[CH:31]=[CH:30][C:29]([S:32]([O:34][CH2:18][CH2:19][CH2:24][NH:22][C:36]([O:39][C:4]([CH3:3])([CH3:5])[CH3:6])=[O:38])(=[O:8])=[O:33])=[CH:28][CH:27]=1

Participants

9

Reactant 6

HCID 73984-Chlorobenzenesulfonyl chlorideHCID 78922-MethylpentaneHCID 8471TriethylamineHCID 8857Ethyl AcetateHCID 516875Potassium PermanganateHCID 10313079Trimethylamine Hydrochloride

Product 1

HCID 866280513-[[(1,1-Dimethylethoxy)carbonyl]amino]propyl 4-chlorobenzenesulfonateYield 32%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
22 °C

Procedure

The reaction was analysed by TLC (3:1 ethyl acetate: isohexane, potassium permanganate stain). The reaction mixture was cooled to 22° C., and triethylamine (27 mL, 193.71 mmol) was added. After further cooling of the reaction mixture to −10° C., trimethylamine hydrochloride (6.45 g, 66.14 mmol) was added and the temperature reduced to −15° C. Stirring was continued at −15° C. for 5 minutes. A solution of 4-chlorobenzenesulfonyl chloride (27.55 g, 130.53 mmol) in DCM (127 mL) was then added over 45 minutes maintaining the temperature at less than −10° C. Once addition was complete, the reaction was stirred at −10° C. for a further 5 minutes before being warmed to 5° C. over 30 minutes. Water (196 mL) was added and the resulting biphasic mixture stirred rapidly for 5 minutes. The phases were then separated and the upper (aqueous) layer discarded. Solvent (186 mL) was removed by distillation under vacuum, keeping the temperature below 40° C. Propan-2-ol (235 mL) was then added. Further solvent (81 mL) was removed by distillation under vacuum (keeping the temperature below 40° C.), after which the mixture was cooled to 20° C. and water (88 mL) added over 60 minutes to crystallise the product from solution. The product was collected by filtration, washed with 1:1 v/v propan-2-ol: water (100 mL), suction dried as far as possible on the filter, then dried in vacuo (35° C., 16 h) to give the title compound as a white solid (14.42 g, 41.22 mmol, 32%).

Workup

  1. temperatureAfter further cooling of the reaction mixture to −10° C.
  2. customreduced to −15° C
  3. temperaturemaintaining the temperature at less than −10° C
  4. additionOnce addition
  5. stirringthe reaction was stirred at −10° C. for a further 5 minutes
  6. temperaturebefore being warmed to 5° C. over 30 minutes
  7. stirringthe resulting biphasic mixture stirred rapidly for 5 minutes
  8. customThe phases were then separated
  9. customSolvent (186 mL) was removed by distillation under vacuum
  10. customthe temperature below 40° C
  11. additionPropan-2-ol (235 mL) was then added
  12. customFurther solvent (81 mL) was removed by distillation under vacuum (
  13. customthe temperature below 40° C.
  14. temperaturewas cooled to 20° C.
  15. additionwater (88 mL) added over 60 minutes
  16. customto crystallise the product from solution
  17. filtrationThe product was collected by filtration
  18. washwashed with 1:1 v/v propan-2-ol
  19. dry with materialwater (100 mL), suction dried as far as possible on the filter
  20. customdried in vacuo (35° C., 16 h)

Sources & evidence

ORD record
ord-1bd4b5db8b414601b8c716b3a9b8b51a
Source dataset
uspto-grants-2011_04
Patent number
US07928225B2

Reaction notes

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