Hydrochloric Acid → (2S)-1-[N-(4-Chlorobenzylaminocarbonyl)-L-prolyl]-2-[2-(4-chlorophenoxy)-1-hydroxyethyl]pyrrolidine

HRID 1720513Notes

Reaction equation

HRID 1720513 reaction equation
ClC(OC(Cl)(Cl)Cl)=O.[Cl:9][C:10]1[CH:17]=[CH:16][C:13]([CH2:14][NH2:15])=[CH:12][CH:11]=1.Cl.ClC1C=CC(OCC([C@@H]2CCCN2C(=O)[C@@H]2CCCN2)O)=CC=1.C([O:46][C:47]([N:49]1[CH2:71][CH2:70][CH2:69][C@H:50]1[C:51]([N:53]1[CH2:57][CH2:56][CH2:55][C@H:54]1[CH:58]([OH:68])[CH2:59][O:60][C:61]1[CH:66]=[CH:65][C:64]([Cl:67])=[CH:63][CH:62]=1)=[O:52])=O)(C)(C)C.Cl>C1COCC1.O1CCOCC1.C(Cl)Cl.C(N(CC)CC)C>[Cl:9][C:10]1[CH:17]=[CH:16][C:13]([CH2:14][NH:15][C:47]([N:49]2[CH2:71][CH2:70][CH2:69][C@H:50]2[C:51]([N:53]2[CH2:57][CH2:56][CH2:55][C@H:54]2[CH:58]([OH:68])[CH2:59][O:60][C:61]2[CH:62]=[CH:63][C:64]([Cl:67])=[CH:65][CH:66]=2)=[O:52])=[O:46])=[CH:12][CH:11]=1

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 10426DiphosgeneHCID 660364-ChlorobenzylamineHCID 67771535(2S)-1-[N-(tert-butoxycarbonyl)-L-prolyl]-2-[2-(4-chlorophenoxy)-l-hydroxyethyl]pyrrolidineHCID 67771646(2S)-2-[2-(4-chlorophenoxy)-1-hydroxyethyl]-1-(L-prolyl)pyrrolidine hydrochloride

Product 1

HCID 67771067(2S)-1-[N-(4-Chlorobenzylaminocarbonyl)-L-prolyl]-2-[2-(4-chlorophenoxy)-1-hydroxyethyl]pyrrolidine

Reagents, catalysts & solvents 4

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent2×HCID 312751,4-DioxaneSolvent

Procedure

To a solution of trichloromethyl chloroformate (0.35 ml) THF (40 ml) was dropwise added a solution of 4-chlorobenzylamine (0.71 ml) and triethylamine (0.81 ml) in THF (20 ml) under ice-cooling, and the mixture was stirred at room temperature for 1.5 hours. A suspension of (2S)-2-[2-(4-chlorophenoxy)-1-hydroxyethyl]-1-(L-prolyl)pyrrolidine hydrochloride which had been obtained by treating (2S)-1-[N-(tert-butoxycarbonyl)-L-prolyl]-2-[2-(4-chlorophenoxy)-l-hydroxyethyl]pyrrolidine (2.13 g) with 4N hydrochloric acid in 1,4-dioxane (20 ml), and triethylamine (0.81 ml) in methylene chloride (20 ml) was dropwise added to the reaction mixture, followed by stirring at room temperature for 1 hour. The reaction mixture was poured into ice-water and extracted with ethyl acetate. The organic layer was washed with 1N hydrochloric acid, saturated aqueous solution of sodium bicarbonate and saturated brine, dried over anhydrous magnesium sulfate, and concentrated. The residue was purified by silica gel column chromatography (eluate: chloroform-methanol) to give 2.09 g of the title compound.

Workup

  1. temperaturecooling
  2. customhad been obtained
  3. additionwas dropwise added to the reaction mixture
  4. stirringby stirring at room temperature for 1 hour
  5. extractionextracted with ethyl acetate
  6. washThe organic layer was washed with 1N hydrochloric acid, saturated aqueous solution of sodium bicarbonate and saturated brine
  7. dry with materialdried over anhydrous magnesium sulfate
  8. concentrationconcentrated
  9. customThe residue was purified by silica gel column chromatography (eluate: chloroform-methanol)

Sources & evidence

ORD record
ord-8396440d29674d1992a6c27d4a990e63
Source dataset
uspto-grants-1996_04
Patent number
US05506256

Reaction notes

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