Dicyclohexylcarbodiimide → HCID 13605234, compound

HRID 1855744Notes

Reaction equation

HRID 1855744 reaction equation
[CH:1]([NH:3][C@H:4]([C:13]([NH:15][C@H:16]([C:31](O)=[O:32])[CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[C:20]([N:24]([CH2:28][CH2:29][Cl:30])[CH2:25][CH2:26][Cl:27])[CH:19]=1)=[O:14])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([F:12])=[CH:8][CH:7]=1)=[O:2].ON1C(=O)CCC1=O.C1(N=C=NC2CCCCC2)CCCCC1.[CH2:57]([O:59][C:60](=[O:67])[C@H:61]([CH2:63][CH2:64][S:65][CH3:66])[NH2:62])[CH3:58]>CN(C)C=O>[CH2:57]([O:59][C:60](=[O:67])[C@H:61]([CH2:63][CH2:64][S:65][CH3:66])[NH:62][C:31](=[O:32])[C@H:16]([CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[C:20]([N:24]([CH2:28][CH2:29][Cl:30])[CH2:25][CH2:26][Cl:27])[CH:19]=1)[NH:15][C:13](=[O:14])[C@H:4]([CH2:5][C:6]1[CH:11]=[CH:10][C:9]([F:12])=[CH:8][CH:7]=1)[NH:3][CH:1]=[O:2])[CH3:58]

Participants

6

Reactant 4

HCID 10868DicyclohexylcarbodiimideHCID 76508Ethyl methioninateHCID 80170N-HydroxysuccinimideHCID 13605232HCID 13605232, compound

Product 1

HCID 13605234HCID 13605234, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
15 °C

Procedure

554 g of N-formyl-p-fluoro-L-phenylalanyl-m-di-(2-chloroethyl)amino-L-phenylalanine are dissolved in 4.5 liters of dimethyl formamide (DMF). The solution is heated slowly for the dissolution step and then cooled to 15° C. While stirring add: 172 g of N-hydroxysuccinimide+225 g of dicyclohexylcarbodiimide+1,235 g-moles of L-methionine ethyl-ester dissolved in DMF. After 16 hours of stirring at room temperature, the precipitated dicylcohexylurea is removed and to the stirred filtrate 18 liters of a mixture of water and ice are added. The white precipitate is filtered, washed with water and completely dried under vacuum. Yield: 710 g (97.2%); m.p.=180°-182° C.; [α]D20 =-7.0°±1° (c=2, DMF).

Workup

  1. temperatureThe solution is heated slowly for the dissolution step
  2. additionadd
  3. stirringAfter 16 hours of stirring at room temperature
  4. customthe precipitated dicylcohexylurea is removed and to the stirred filtrate 18 liters of a mixture of water and ice
  5. additionare added
  6. filtrationThe white precipitate is filtered
  7. washwashed with water
  8. customcompletely dried under vacuum
  9. custom[α]D20 =-7.0°±1° (c=2, DMF)

Sources & evidence

ORD record
ord-967cc5ca812d4226aae5ea9146060b18
Source dataset
uspto-grants-1980_08
Patent number
US04216208

Reaction notes

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