4-Methylmorpholine → HCID 561963, compound

HRID 1649537Notes

Reaction equation

HRID 1649537 reaction equation
N[C@H](C([NH:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][NH:17][C:18]([O:20][CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)=[O:19])=O)CC(C)C.ON1C2C=CC=CC=2N=N1.CN1CCOCC1.Cl.C(N=C=NCCCN(C)C)C>O1CCCC1>[CH2:21]([O:20][C:18]([NH:17][CH2:16][CH2:15][CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][NH2:9])=[O:19])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 13231864HCID 13231864, compound

Product 1

HCID 561963HCID 561963, compoundYield 67%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

In 80 ml of the tetrahydrofuran were dissolved 1.00 g of DL-trans-benzylhydrogenepoxysuccinate, 1.70 g of N-L-leucyl-N'-benzyloxycarbonyl-1,7-diaminoheptane, 0.73 g of 1-hydroxybenzotriazole and 0.55 g of N-methylmorpholine. To the solution was slowly added 0.95 g of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride under ice-cooling with stirring. The mixture was stirred for 2 hours under ice-cooling and then for 2 hours at room temperature. The solution was concentrated under reduced pressure and admixed with 100 ml of ethyl acetate and 100 ml of water and the mixture was shaken vigorously. The ethyl acetate layer was separated and washed successively with a 10% aqueous hydrochloric acid solution, an aqueous saturated bicarbonate solution and an aqueous saturated sodium chloride solution and concentrated to dryness. The resulting residue was purified by column chromatography on silica gel (chloroform:acetone=10:1) and recrystallized from ethyl acetate-n-hexane to give 1.50 g of N-[N-DL-3-trans-benzyloxycarboxyloxirane-2-carbonyl)-L-leucyl]-N'-benzyloxycarbonyl-1,7-diaminoheptane m.p. 134° C. Yield: 67%.

Workup

  1. temperaturecooling
  2. stirringThe mixture was stirred for 2 hours under ice-
  3. temperaturecooling
  4. concentrationThe solution was concentrated under reduced pressure
  5. stirringthe mixture was shaken vigorously
  6. customThe ethyl acetate layer was separated
  7. washwashed successively with a 10% aqueous hydrochloric acid solution
  8. concentrationan aqueous saturated bicarbonate solution and an aqueous saturated sodium chloride solution and concentrated to dryness
  9. customThe resulting residue was purified by column chromatography on silica gel (chloroform:acetone=10:1)
  10. customrecrystallized from ethyl acetate-n-hexane

Sources & evidence

ORD record
ord-9b5cd19c2df642d99e0486346a5db261
Source dataset
uspto-grants-1983_11
Patent number
US04418075

Reaction notes

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