Dicyclohexylamine → HCID 12876499, compound

HRID 444593Notes

Reaction equation

HRID 444593 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([C:25]([NH:27][C@@H:28]([C:30]([NH:32][CH2:33][C:34]([OH:36])=O)=[O:31])[CH3:29])=[O:26])[CH2:10][C:11]1[CH:16]=[CH:15][C:14]([O:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[CH:13][CH:12]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH2:37][C@H:38]([C:46]([O:48][CH3:49])=[O:47])[CH2:39][C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1.C1(NC2CCCCC2)CCCCC1.C1CCC(N=C=NC2CCCCC2)CC1>CN(C=O)C>[C:1]([O:5][C:6]([NH:8][C@H:9]([C:25]([NH:27][C@@H:28]([C:30]([NH:32][CH2:33][C:34]([NH:37][C@H:38]([C:46]([O:48][CH3:49])=[O:47])[CH2:39][C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1)=[O:36])=[O:31])[CH3:29])=[O:26])[CH2:10][C:11]1[CH:12]=[CH:13][C:14]([O:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[CH:15][CH:16]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 7582DicyclohexylamineHCID 10868DicyclohexylcarbodiimideHCID 736234L-Phenylalanine, methyl esterHCID 11134873HCID 11134873, compound

Product 1

HCID 12876499HCID 12876499, compoundYield 82%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To 30 ml. of DMF were added 2.5 gms. (0.005 moles) of Nα -t-butyloxycarbonyl-O-benzyl-L-tyrosyl-D-alanyl-glycine (prepared as in Example 1) and 1.08 gms. (0.005 moles) of the hydrochloride salt of L-phenylalanine, methyl ester. The mixture was stirred at 0° C., and 0.99 ml. (0.005 moles) of dicyclohexylamine was added. The mixture was stirred for 5 minutes at 0° C., and 670 mg. (0.005 mmoles) of HBT and 1.03 gms. (0.005 moles) of DCC were added. Stirring was continued at 0° C. for 2 hours and then at room temperature for 48 hours. The reaction mixture was cooled to 0° C., and the resulting precipitate was collected. The filtrate was concentrated in vacuo. The residue was dissolved in ethyl acetate, and the ethyl acetate solution was extracted successively with 1 N sodium bicarbonate, water, 0.75 N citric acid, and water. The ethyl acetate solution was dried over magnesium sulfate and concentrated in vacuo. The resulting oil was crystallized from ether and recrystallized from ethyl acetate to give 2.7 grams (82%) of the title compound, m.p. 149°-152° C. [α]D25 +22° (C=0.5, MeOH).

Workup

  1. stirringThe mixture was stirred for 5 minutes at 0° C.
  2. stirringStirring
  3. waitat room temperature for 48 hours
  4. temperatureThe reaction mixture was cooled to 0° C.
  5. customthe resulting precipitate was collected
  6. concentrationThe filtrate was concentrated in vacuo
  7. dissolutionThe residue was dissolved in ethyl acetate
  8. extractionthe ethyl acetate solution was extracted successively with 1 N sodium bicarbonate, water, 0.75 N citric acid, and water
  9. dry with materialThe ethyl acetate solution was dried over magnesium sulfate
  10. concentrationconcentrated in vacuo
  11. customThe resulting oil was crystallized from ether
  12. customrecrystallized from ethyl acetate

Sources & evidence

ORD record
ord-f36af1f0c6ba4cc79e10cd5b4f7447ae
Source dataset
uspto-grants-1981_04
Patent number
US04264491

Reaction notes

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