4-Chlorobenzenesulfonyl chloride → HCID 56953106, compound

HRID 660268Notes

Reaction equation

HRID 660268 reaction equation
Cl.[NH2:2][C@H:3]([CH2:7][CH2:8][C:9]([F:12])([F:11])[F:10])[C:4]([NH2:6])=[O:5].[Cl:13][C:14]1[CH:19]=[CH:18][C:17]([S:20](Cl)(=[O:22])=[O:21])=[CH:16][CH:15]=1.C1COCC1.C(N(CC)CC)C>O>[Cl:13][C:14]1[CH:19]=[CH:18][C:17]([S:20]([NH:2][C@H:3]([CH2:7][CH2:8][C:9]([F:10])([F:11])[F:12])[C:4]([NH2:6])=[O:5])(=[O:22])=[O:21])=[CH:16][CH:15]=1

Participants

6

Reactant 4

HCID 73984-Chlorobenzenesulfonyl chlorideHCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 70700839(R)-2-Amino-5,5,5-trifluoropentanamide hydrochloride

Product 1

HCID 56953106HCID 56953106, compoundYield 91%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
20 °C

Procedure

To a suitable dry vessel was added (R)-2-amino-5,5,5-trifluoropentanamide hydrochloride (199.52 g 0.966 mol, 1.0 equiv) followed by 4-chlorobenzenesulfonyl chloride (215.22 g 0.989 mol, 1.02 equiv, 97% w/w %) and 1.6 L of THF at room temperature. Triethylamine (206.5 g, 2.04 mol, 2.1 equiv.) was added over 20 min, maintaining the pot temperature at 15-25° C., and the resulting white slurry was stirred at 15-25° C. for 30 min. Water (1.4 L, 7 vol) of was added to the reaction mixture at 20-25° C. and then THF (1.4 L, 7 vol) was removed by distillation under vacuum (the pot temperature was maintained at 40-60° C. under 250-400 mmHg during distillation process). When the distillation process was complete, 1.4 L (7 vol) of water was added over 30 min while maintaining the pot temperature at 50-60° C., and the resulting slurry was stirred at 50-60° C. for 30 min and then cooled to 10° C. The slurry was agitated for not less than 1 hour, and the product was filtered. The filter cake was washed with water (600 mL each wash) until the pH of the cake wash measured ≧5. The cake was dried under vacuum at not more than 70° C. (jacket temp.) until the loss on drying is <0.5 w/w %, giving the title compound as a white solid (300 g, 91% yield.) 1H NMR (DMSO-d6) (400 MHz) δ 160-1.90 (two m, 1H each of CH2), 2.10-2.35 (m, 2H of CH2—CF3), 3.85-3.88 (m,1H, —(CONH2)CH(NH), 7.13 & 7.37 (br s, 1H, each of CONH2), 7.61 (m, 2H, Ar—Ha), 7.64 (m, 2H, Ar—Hb), 8.18 (d, 1H, J=8.0 Hz, NH—SO2). 13C NMR (DMSO-d6) (100.0 MHz) δ 171.75, 140.27, 137.77, 131.71, 129.56, 128.95, 126.22, 55.12, 30.1, 29.82, 29.53, 29.25, 25.82, 25.79.

Workup

  1. customTHF (1.4 L, 7 vol) was removed by distillation under vacuum (the pot temperature
  2. temperaturewas maintained at 40-60° C. under 250-400 mmHg during distillation process)
  3. addition1.4 L (7 vol) of water was added over 30 min
  4. temperaturewhile maintaining the pot temperature at 50-60° C.
  5. stirringthe resulting slurry was stirred at 50-60° C. for 30 min
  6. temperaturecooled to 10° C
  7. stirringThe slurry was agitated for not less than 1 hour
  8. filtrationthe product was filtered
  9. washThe filter cake was washed with water (600 mL each wash) until the pH of the cake
  10. washwash
  11. customThe cake was dried under vacuum at not more than 70° C. (jacket temp.) until the loss
  12. customon drying

Sources & evidence

ORD record
ord-cd310bbb95f54c33bbb0a127de01479d
Source dataset
uspto-grants-2011_12
Patent number
US08084477B2

Reaction notes

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