Benzylamine → (S)-1-benzyl-3-(p-toluenesulfonylamino)pyrrolidine

HRID 1646042Notes

Reaction equation

HRID 1646042 reaction equation
CS(O[CH2:6][CH2:7][CH:8]1[CH2:10][N@@:9]1[S:11]([C:14]1[CH:19]=[CH:18][C:17]([CH3:20])=[CH:16][CH:15]=1)(=[O:13])=[O:12])(=O)=O.[CH2:21]([NH2:28])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.C(N(CC)CC)C>O1CCCC1.CS(C)=O>[CH2:21]([N:28]1[CH2:6][CH2:7][C@H:8]([NH:9][S:11]([C:14]2[CH:19]=[CH:18][C:17]([CH3:20])=[CH:16][CH:15]=2)(=[O:13])=[O:12])[CH2:10]1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1

Participants

6

Reactant 3

HCID 7504BenzylamineHCID 8471TriethylamineHCID 178427310HCID 178427310, compound

Product 1

HCID 10782668(S)-1-benzyl-3-(p-toluenesulfonylamino)pyrrolidine

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8028TetrahydrofuranSolvent

Procedure

(S)-2-(2'-Methanesulfonyloxyethyl)-1-(p-toluenesulfonyl)aziridine, 3, (54.5 g) was dissolved in warm tetrahydrofuran (50 mL) and the solution added dropwise over 20 minutes to a solution of benzylamine (40 g) and triethylamine (40 g) in dimethyl sulfoxide (250 mL) at 75° to 85° C. The resulting solution was heated another 2.5 hours at 75° to 85° C. and then concentrated under vacuum to remove tetrahydrofuran and dimethyl sulfoxide. The residue was dissolved in toluene (300 mL) and cautiously treated with 10 g of dry ice followed by 1.0 N NaOH (150 mL). The layers were separated and the toluene layer treated cautiously with more dry ice (3 g) followed by 20 mL 1.0 N NaOH. This carbon dioxide NaOH extraction procedure was repeated three more times and the resulting toluene solution concentrated under vacuum to give (S)-1-benzyl-3-(p-toluenesulfonylamino)pyrrolidine, 4, as an amber oil. The oil was dissolved in warm (60°-70° C.) toluene (15 mL) and a solution (30 mL) of isopropyl alcohol saturated with hydrogen chloride gas was added. The solution was stirred and cooled to -5° C. where it was maintained for 3 hours. The solid product was collected and washed with isopropyl alcohol and ether and vacuum dried to give (S) 1-benzyl-3-(p-toluenesulfonylamino)pyrrolidine hydrochloride as an off-white solid (46.5 g, 74% combined yield for Steps 3 and 4). A portion was recrystallized from isopropyl alcohol: mp 179°-181° C.

Workup

  1. temperatureThe resulting solution was heated another 2.5 hours at 75° to 85° C.
  2. concentrationconcentrated under vacuum
  3. customto remove tetrahydrofuran and dimethyl sulfoxide
  4. dissolutionThe residue was dissolved in toluene (300 mL)
  5. additioncautiously treated with 10 g of dry ice
  6. customThe layers were separated
  7. additionthe toluene layer treated cautiously with more dry ice (3 g)
  8. extractionThis carbon dioxide NaOH extraction procedure
  9. concentrationthe resulting toluene solution concentrated under vacuum

Sources & evidence

ORD record
ord-35e165b2e5dd43a28d0ff4b3b35b5ac9
Source dataset
uspto-grants-1993_01
Patent number
US05177217

Reaction notes

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