4-Methylmorpholine → HCID 12877299, compound

HRID 2413115Notes

Reaction equation

HRID 2413115 reaction equation
Cl.[CH3:2][O:3][C:4](=[O:8])[C@@H:5]([CH3:7])[NH2:6].CN1CCOCC1.[CH2:16]([O:23][C:24]([NH:26][C@H:27]([C:35](O)=[O:36])[CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)=[O:25])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.ON1C2C=CC=CC=2N=N1.C1(N=C=NC2CCCCC2)CCCCC1>O1CCCC1.C(O)(=O)C>[CH3:2][O:3][C:4](=[O:8])[C@@H:5]([CH3:7])[NH:6][C:35](=[O:36])[C@H:27]([CH2:28][C:29]1[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1)[NH:26][C:24]([O:23][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=[O:25]

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 10868DicyclohexylcarbodiimideHCID 70878Benzyloxycarbonyl-L-phenylalanineHCID 757711-HydroxybenzotriazoleHCID 11182647Methyl D-alaninate hydrochloride

Product 1

HCID 12877299HCID 12877299, compound

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

First benzyloxycarbonyl-L-phenylalanyl-D-alanine methyl ester was prepared, as follows. A solution of 0.56 g of D-alanine methyl ester hydrochloride in 6 ml tetrahydrofuran was cooled to 0° C. and then treated with 0.53 ml of N-methylmorpholine. After 15 min of stirring, 1.20 g of benzyloxycarbonyl-L-phenylalanine and 1.08 g of 1-hydroxybenzotriazole were added. A cold solution of 0.99 g of N, N'-dicyclohexylcarbodiimide in 2 ml tetrahydrofuran was then added and the mixture stirred for 1 hour at 0° C., then overnight at room temperature. After adding 0.3 ml of glacial acetic acid, the mixture was stirred 5 min., filtered, and the filtrate concentrated in vacuo to dryness. The residue was dissolved in CHCl3, washed 3 times with 5% aqueous NaHCO3, dried over anhydrous Na2SO4, and the solvent removed in vacuo. The residue was purified by silica gel column chromatography (silica 60 g) using CHCl3 followed by CHCl3 -acetone 10:1 as eluant. Appropriate fractions were pooled and the solvent removed in vacuo to obtain 0.74 g of white solid, m.p. 134-136 C. TLC on silica gel using an eluant of 10 acetone gave Rf =0.37.

Workup

  1. stirringthe mixture stirred for 1 hour at 0° C.
  2. customovernight
  3. customat room temperature
  4. stirringthe mixture was stirred 5 min.
  5. filtrationfiltered
  6. concentrationthe filtrate concentrated in vacuo to dryness
  7. dissolutionThe residue was dissolved in CHCl3
  8. washwashed 3 times with 5% aqueous NaHCO3
  9. dry with materialdried over anhydrous Na2SO4
  10. customthe solvent removed in vacuo
  11. customThe residue was purified by silica gel column chromatography (silica 60 g)
  12. customthe solvent removed in vacuo

Sources & evidence

ORD record
ord-6f0c933b09324677ad90a2792c05a1d1
Source dataset
uspto-grants-1985_01
Patent number
US04496540

Reaction notes

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