4-Methylmorpholine → HCID 178450981, compound

HRID 36804

Reaction equation

HRID 36804 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C@H:12]([C:17]([OH:19])=O)[CH2:13][CH:14]([CH3:16])[CH3:15])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CN1CCOCC1.ClC(OCC(C)C)=O.Cl.[CH2:36]([O:40][CH:41]([O:51][CH2:52][CH2:53][CH2:54][CH3:55])[C@H:42]([CH2:44][CH2:45][CH2:46][NH:47][C:48](=[NH:50])[NH2:49])[NH2:43])[CH2:37][CH2:38][CH3:39]>CN(C)C=O.C(N(CC)CC)C>[CH2:52]([O:51][CH:41]([O:40][CH2:36][CH2:37][CH2:38][CH3:39])[C@H:42]([CH2:44][CH2:45][CH2:46][NH:47][C:48](=[NH:49])[NH2:50])[NH:43][C:17](=[O:19])[C@H:12]([CH2:13][CH:14]([CH3:15])[CH3:16])[NH:11][C:9]([O:8][CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)=[O:10])[CH2:53][CH2:54][CH3:55]

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 74840Leucine, N-carboxy-, N-benzyl ester, L-HCID 178450993HCID 178450993, compound

Product 1

HCID 178450981HCID 178450981, compoundYield 69.7%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8471TriethylamineSolvent

Conditions

Temperature
-15 °C

Procedure

In 25 ml of dimethylformamide was dissolved 2.65 g of N-benzyloxycarbonyl-L-leucine. After cooling to -15° C., 1.10 ml of N-methylmorpholine and then 1.37 ml of isobutyl chloroformate were added to the solution while stirring the solution at the same temperature. The mixture was sitrred at -15° C. for 5 minutes. On the other hand, 3.25 g of L-argininal dibutyl acetal hydrochloride (Example 2) was dissolved in 30 ml of dimethylformamide and 1.40 ml of triethylamine was added to the solution. The resulting solution was dropwise added at -10° C. to the mixed acid anhydride suspension which had been previously prepared. Stirring was continued at the same temperature for an hour and then at 0° C. for an hour. The resulting reaction solution was concentrated under reduced pressure and the residue was dissolved in 100 ml of chloroform. The solution was washed successively with 10% citric acid aqueous solution (30 ml×2), saturated sodium chloride aqueous solution (30 ml×1), saturated sodium hydrogencarbonate aqueous solution (30 ml×2) and saturated sodium chloride aqueous solution (30 ml×2). After drying over anhydrous magnesium sulfate, the solvent was distilled off under reduced pressure. The obtained residue was subjected to column chromatography using silica gel as a carrier and developed with chloroform: methanol=20:1 (v/v). The fraction showing Rf: 0.48 (under the same conditions as in Example 1 (A) 4) which was positive in the Sakaguchi reaction, was concentrated under reduced pressure to give 3.73 g of N-benzyloxycarbonyl-L-leucyl-L-argininal dibutyl acetal.

Workup

  1. customhad been previously prepared
  2. stirringStirring
  3. waitwas continued at the same temperature for an hour
  4. waitat 0° C. for an hour
  5. customThe resulting reaction solution
  6. concentrationwas concentrated under reduced pressure
  7. dissolutionthe residue was dissolved in 100 ml of chloroform
  8. washThe solution was washed successively with 10% citric acid aqueous solution (30 ml×2), saturated sodium chloride aqueous solution (30 ml×1), saturated sodium hydrogencarbonate aqueous solution (30 ml×2) and saturated sodium chloride aqueous solution (30 ml×2)
  9. dry with materialAfter drying over anhydrous magnesium sulfate
  10. distillationthe solvent was distilled off under reduced pressure
  11. customwas positive in the Sakaguchi reaction
  12. concentrationwas concentrated under reduced pressure

Sources & evidence

ORD record
ord-6b218140444744549e981b24dba79eb8
Source dataset
uspto-grants-1995_05
Patent number
US05416238

Linked notes

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