Dicyclohexylcarbodiimide → HCID 86739930, compound

HRID 615680Notes

Reaction equation

HRID 615680 reaction equation
[C:1]([NH:5][C@H:6]([C:8]([N:10]1[CH2:17][CH2:16][CH2:15][C@H:11]1[C:12]([OH:14])=[O:13])=[O:9])[CH3:7])([CH3:4])([CH3:3])[CH3:2].C(OC(N[C@H](C(O)=O)C)=O)C1C=CC=CC=1.C(N1CCC[C@H]1C(O)=O)(C)(C)C.C1(N=C=NC2CCCCC2)CCCCC1.[C:61]([NH:69][CH:70]([S:74][C:75](=[O:82])[C:76]1[CH:81]=[CH:80][CH:79]=[CH:78][CH:77]=1)[C:71](O)=[O:72])(=[O:68])[C:62]1[CH:67]=[CH:66][CH:65]=[CH:64][CH:63]=1>C(#N)C.O1CCCC1>[C:1]([N:5]([C:71](=[O:72])[CH:70]([S:74][C:75](=[O:82])[C:76]1[CH:77]=[CH:78][CH:79]=[CH:80][CH:81]=1)[NH:69][C:61](=[O:68])[C:62]1[CH:67]=[CH:66][CH:65]=[CH:64][CH:63]=1)[C@H:6]([C:8]([N:10]1[CH2:17][CH2:16][CH2:15][C@H:11]1[C:12]([OH:14])=[O:13])=[O:9])[CH3:7])([CH3:2])([CH3:3])[CH3:4]

Participants

8

Reactant 5

HCID 10868Dicyclohexylcarbodiimide2×HCID 736104N-carbobenzyloxyalanineHCID 13316791N-benzoyl-alpha-(benzoylthio)-glycineHCID 54302920HCID 54302920, compoundHCID 70536985HCID 70536985, compound

Product 1

HCID 86739930HCID 86739930, compoundYield 75%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolvent

Procedure

12.1 g (50 millimoles) of tert.-butyl alanylproline (prepared by coupling benzyloxycarbonylalanine with tert.-butyl proline using dicyclohexylcarbodiimide, followed by hydrogenolytic elimination of the protective group) were dissolved in 150 ml of dry acetonitrile, a solution of 15.8 g (50 millimoles) of N-benzoyl-α-(benzoylthio)-glycine in 150 ml of dry tetrahydrofuran and 10.3 g (50 millimoles) of dicyclohexylcarbodiimide were added and the mixture was stirred overnight at room temperature. The precipitated dicyclohexylurea was filtered off under suction, and the filtrate was evaporated down under reduced pressure. The residue was chromatographed with 1:1 cyclohexane/ethyl acetate over a column containing deactivated silica gel. 20.2 g (75%) of tert.-butyl N-[N-benzoyl-α-(benzoylthio)glycyl]-alanylproline were obtained as a diastereomer mixture. Crystallization from cyclohexane/ethyl acetate gave 7.5 g of a low-melting isomer of melting point 97°-100° C.; 7.8 g of a high-melting isomer of melting point 147°-150° C. were obtained from the mother liquor after crystallizing the product twice from cyclohexane/ethyl acetate. Cleavage of the two isomers separately, using 6 N HCl/dioxane in a procedure similar to that described in Example 1b, gave N-[N-benzoyl-α-(benzoylthio)-glycyl]-alanylproline as diastereomer I (obtained in crystalline form from ethyl acetate, melting point 185°-188° C., Rf=0.18 in system I, [α]D20 =+29° (c=1 in chloroform)) and diastereomer II (obtained in crystalline form from ethyl acetate, melting point 203°-206° C., Rf=0.18 in system I, [α]D20 =-167° (c=1 in chloroform)).

Workup

  1. filtrationThe precipitated dicyclohexylurea was filtered off under suction
  2. customthe filtrate was evaporated down under reduced pressure
  3. customThe residue was chromatographed with 1:1 cyclohexane/ethyl acetate over a column
  4. additioncontaining deactivated silica gel

Sources & evidence

ORD record
ord-108ec29aa15445a58bd7d75f66b630a8
Source dataset
uspto-grants-1985_02
Patent number
US04500467

Reaction notes

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