Propane sultone → 3-{[(1S)-1-(benzyloxycarbonyl)-3-methylbutyl]amino}-1-propanesulfonic acid

HRID 239776Notes

Reaction equation

HRID 239776 reaction equation
[CH2:1]([O:8][C:9](=[O:16])[C@H:10]([CH2:12][CH:13]([CH3:15])[CH3:14])[NH2:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:17]1[CH2:23][S:20](=[O:22])(=[O:21])[O:19][CH2:18]1>O1CCCC1.O1CCOCC1.CO>[CH2:1]([O:8][C:9]([C@@H:10]([NH:11][CH2:18][CH2:17][CH2:23][S:20]([OH:22])(=[O:21])=[O:19])[CH2:12][CH:13]([CH3:14])[CH3:15])=[O:16])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 2

HCID 14264Propane sultoneHCID 6451313Benzyl L-leucinate

Product 1

HCID 160361753-{[(1S)-1-(benzyloxycarbonyl)-3-methylbutyl]amino}-1-propanesulfonic acidYield 47.3%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of L-Leucine benzylester (2.81 g, 12.7 mmol) in tetrahydrofuran (6 mL), 1,4-dioxane (6 mL) and MeOH (6 mL) was added 1,3-propane sultone (1.40 g, 11.5 mmol). The solution was stirred at reflux for 2.5 hours. The reaction mixture was cooled to room temperature. The solid was filtered and washed with acetone (2×20 mL). The filtrate was evaporated under reduced pressure. The residue was dissolved in acetone (20 mL). The product was precipitated with Et2O (200 mL). The solid material was filtered. Both solids were combined and dissolved in 50% EtOH/water (200 mL). Dowex Marathon C ion exchange resin (strongly acidic) was added to the solution. The suspension was stirred for 15 minutes before the resin was removed by filtration. The filtrate was evaporated under reduced pressure and lyophilized, affording the title compound (1.87 g, 47%). 1H NMR (DMSO, 500 MHz) δ ppm 9.34 (s (broad), 1H), 7.39 (m, 5H), 5.25 (s, 2H), 4.10 (m, 1H), 3.09 (m, 2H), 2.60 (m, 2H), 1.95 (m, 2H), 1.64 (m, 3H), 0.86 (m, 6H). 13C (DMSO, 125 MHz) δ ppm 168.90, 134.91, 128.53, 128.50, 128.41, 67.38, 57.37, 49.17, 45.79, 38.06, 24.07, 22.79, 21.78, 21.33. [α]D=+1.8° (c=0.0017 in water), ES-MS 344 (M+1).

Workup

  1. temperatureat reflux for 2.5 hours
  2. filtrationThe solid was filtered
  3. washwashed with acetone (2×20 mL)
  4. customThe filtrate was evaporated under reduced pressure
  5. dissolutionThe residue was dissolved in acetone (20 mL)
  6. customThe product was precipitated with Et2O (200 mL)
  7. filtrationThe solid material was filtered
  8. dissolutiondissolved in 50% EtOH/water (200 mL)
  9. additionDowex Marathon C ion exchange resin (strongly acidic) was added to the solution
  10. stirringThe suspension was stirred for 15 minutes before the resin
  11. customwas removed by filtration
  12. customThe filtrate was evaporated under reduced pressure

Sources & evidence

ORD record
ord-04fd9f963bb0482da099331b33cf34dd
Source dataset
uspto-grants-2014_02
Patent number
US08642801B2

Reaction notes

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