Hydrochloric Acid → (2S,4S)-2-(4-carbamoylpiperazin-1-yl)methyl-1-(4-nitrobenzyloxycarbonyl)-4-(triphenylmethylthio)pyrrolidine

HRID 1650849Notes

Reaction equation

HRID 1650849 reaction equation
CS(O[CH2:6][C@@H:7]1[CH2:11][C@H:10]([S:12][C:13]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH2:9][N:8]1[C:32]([O:34][CH2:35][C:36]1[CH:41]=[CH:40][C:39]([N+:42]([O-:44])=[O:43])=[CH:38][CH:37]=1)=[O:33])(=O)=O.[NH:45]1[CH2:50][CH2:49][NH:48][CH2:47][CH2:46]1.Cl.[O-:52][C:53]#[N:54].[K+]>CN(C)C=O.O1CCCC1.O.C(OCC)(=O)C>[C:53]([N:45]1[CH2:50][CH2:49][N:48]([CH2:6][C@@H:7]2[CH2:11][C@H:10]([S:12][C:13]([C:26]3[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=3)([C:20]3[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=3)[C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=3)[CH2:9][N:8]2[C:32]([O:34][CH2:35][C:36]2[CH:37]=[CH:38][C:39]([N+:42]([O-:44])=[O:43])=[CH:40][CH:41]=2)=[O:33])[CH2:47][CH2:46]1)(=[O:52])[NH2:54]

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 4837PiperazineHCID 11378442Potassium cyanateHCID 15056119(2S,4S)-2-mesyloxymethyl-N-(p-nitrobenzyloxycarbonyl)-4-tritylthiopyrrolidine

Product 1

HCID 15056153(2S,4S)-2-(4-carbamoylpiperazin-1-yl)methyl-1-(4-nitrobenzyloxycarbonyl)-4-(triphenylmethylthio)pyrrolidineYield 54.2%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of (2S,4S)-2-(methanesulfonyloxy)methyl-1-(4-nitrobenzyloxycarbonyl)-4-(triphenylmethylthio)pyrrolidine (2.28 g) and piperazine (0.93 g) in dimethylformamide (40 ml) was stirred at 80°-90° C. for 5 hours. The reaction mixture was poured into ice-water (150 ml). The precipitates were collected by filtration, washed with water and dissolved in ethyl acetate (100 ml). The solution was washed twice with saturated aqueous sodium chloride (30 ml), dried over anhydrous magnesium sulfate and evaporated in vacuo to give a residue. The residue was dissolved in a mixture of tetrahydrofuran (20 ml) and water (10 ml). To the solution were added concentrated hydrochloric acid (0.60 ml) and potassium cyanate (0.44 g) and the mixture was stirred at 50° C. for 30 minutes. Ethyl acetate was added to the reaction mixture with stirring. The organic layer was separated and washed twice with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and evaporated in vacuo. The resulting residue was chromatographed on silica gel (100 g) eluting with a mixture of dichloromethane and acetone (2:1, V/V and then 1:2, V/V). The fractions containing the desired compound were collected and evaporated in vacuo to give (2S,4S)-2-(4-carbamoylpiperazin-1-yl)methyl-1-(4-nitrobenzyloxycarbonyl)-4(triphenylmethylthio)pyrrolidine (1.30 g).

Workup

  1. filtrationThe precipitates were collected by filtration
  2. washwashed with water
  3. dissolutiondissolved in ethyl acetate (100 ml)
  4. washThe solution was washed twice with saturated aqueous sodium chloride (30 ml)
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customevaporated in vacuo
  7. customto give a residue
  8. stirringthe mixture was stirred at 50° C. for 30 minutes
  9. stirringwith stirring
  10. customThe organic layer was separated
  11. washwashed twice with saturated aqueous sodium chloride
  12. dry with materialdried over anhydrous magnesium sulfate
  13. customevaporated in vacuo
  14. customThe resulting residue was chromatographed on silica gel (100 g)
  15. washeluting with a mixture of dichloromethane and acetone (2:1, V/V
  16. additionThe fractions containing the desired compound
  17. customwere collected
  18. customevaporated in vacuo

Sources & evidence

ORD record
ord-2927ad15322e4d2aa45e05635334ef38
Source dataset
uspto-grants-1990_05
Patent number
US04925838

Reaction notes

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