1-Cyclohexyl-3-(2-morpholinoethyl)carbodiimide metho-p-toluenesulfonate → HCID 7055495, compound

HRID 703196Notes

Reaction equation

HRID 703196 reaction equation
[CH3:1][C:2]([CH3:19])([O:4][C:5]([NH:7][C@H:8]([C:16]([OH:18])=O)[CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)=[O:6])[CH3:3].Cl.[NH2:21][C@H:22]([C:27]([O:29][CH3:30])=[O:28])[CH2:23][CH:24]([CH3:26])[CH3:25].O.OC1C2N=NNC=2C=CC=1.C(N(C(C)C)CC)(C)C.CC1C=CC(S([O-])(=O)=O)=CC=1.C[N+]1(CCN=C=NC2CCCCC2)CCOCC1>CN(C)C=O>[CH3:19][C:2]([CH3:1])([O:4][C:5]([NH:7][C@H:8]([C:16]([NH:21][C@H:22]([C:27]([O:29][CH3:30])=[O:28])[CH2:23][CH:24]([CH3:26])[CH3:25])=[O:18])[CH2:9][C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1)=[O:6])[CH3:3]

Participants

7

Reactant 5

HCID 172201-Cyclohexyl-3-(2-morpholinoethyl)carbodiimide metho-p-toluenesulfonateHCID 77857L-Phenylalanine, N-[(1,1-dimethylethoxy)carbonyl]-HCID 81531DiisopropylethylamineHCID 2723695Leucine methyl ester hydrochlorideHCID 178526939HCID 178526939, compound

Product 1

HCID 7055495HCID 7055495, compoundYield 81.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a solution containing N-[(1,1-Dimethylethoxy)carbonyl]-L-phenylalanine (19.89 g, 75 mmol) in dry dimethylformamide (375 mL) was added L-leucine, methyl ester, monohydrochloride (13.62 g, 75 mmol) and hydroxybenzotriazole hydrate (11.46 g, 75 mmol). The resulting mixture was cooled to 0° C. under argon and treated with diisopropylethylamine (9.69 g, 13 mL, 75 mmol) followed by 1-cyclohexyl-3-(2-morpholinoethyl) carbodiimide metho-p-toluenesulfonate (33.5 g, 75 mmol). The reaction was allowed to warm to ambient temperature overnight, then concentrated in vacuo to half volume followed by treatment with 800 ml of pH 4 phosphate buffer. A white solid that separated from solution was collected by filtration and dissolved in ethyl acetate (600 mL). The organic solution was rinsed with saturated aqueous sodium hydrogen carbonate, water and brine, then dried over anhydrous magnesium sulfate and concentrated in vacuo to give 24 g of crude product. The entire product was dissolved in hot diisopropyl ether (250 mL) and the resulting solution concentrated to about half volume and refrigerated overnight. By this method, 22.2 g of the title A compound was obtained from the first crop with an additional 1.1 g from the mother liquor, m.p. 105°-106° C.

Workup

  1. temperatureto warm to ambient temperature overnight
  2. concentrationconcentrated in vacuo to half volume
  3. customA white solid that separated from solution
  4. filtrationwas collected by filtration
  5. dissolutiondissolved in ethyl acetate (600 mL)
  6. washThe organic solution was rinsed with saturated aqueous sodium hydrogen carbonate, water and brine
  7. dry with materialdried over anhydrous magnesium sulfate
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-babf171207924aeabd782942a8d04d6d
Source dataset
uspto-grants-1991_01
Patent number
US04981843

Reaction notes

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