4-Methylmorpholine → HCID 54023474, compound

HRID 1898958Notes

Reaction equation

HRID 1898958 reaction equation
[C:1]([NH:20][C@H:21]([C:29]([OH:31])=O)[CH2:22]C1C=CC=CC=1)([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)(C1C=CC=CC=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.ON1[C:37]2[CH:38]=[CH:39][CH:40]=[CH:41][C:36]=2N=N1.C1(N=C=N[CH:51]2[CH2:56][CH2:55][CH2:54][CH2:53][CH2:52]2)CCCCC1.C1(C)C=CC(S(O)(=O)=O)=CC=1.[CH2:68]([O:70][C:71](=[O:82])[CH2:72][NH:73][C:74](=[O:81])[C@H:75]([CH2:77][CH:78]([CH3:80])[CH3:79])[NH2:76])[CH3:69].CN1CCOCC1>O1CCCC1>[CH2:68]([O:70][C:71](=[O:82])[CH2:72][NH:73][C:74](=[O:81])[C@H:75]([CH2:77][CH:78]([CH3:79])[CH3:80])[NH:76][C:29](=[O:31])[C@H:21]([CH2:22][C:51]1[CH:52]=[CH:53][CH:54]=[CH:55][CH:56]=1)[NH:20][C:1]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)([C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)[CH3:69]

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 7353749HCID 7353749, compoundHCID 22866696HCID 22866696, compound

Product 1

HCID 54023474HCID 54023474, compoundYield 60.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

N-trityl-L-Phenylalanine (20.3 g, 50 mmo1), prepared as described in J.Org. Chem. 47, 1324 (1982) was dissolved in anhydrous terahydrofurane (150 ml) and added with anhydrous N-hydroxybenzotriazole (8 gr). The mixture was cooled at 0° C. and treated with 1,3-dicyclohexylcarbodiimide (11.7 gr, 50 mmol) and, after 10 minutes, added dropwise with a solution of L-Leucylglycine ethylester p-toluensulphonate salt (20 g, 50 mmol) in in a mixture of anhydrous tetrahydrofurane (100 ml) and N-methylmorpholine (7 ml). The reaction mixture was kept at 0° C. for one hour and overnight at room temperature, then was filtered and the solvent was removed under reduced pressure. The crude material, dissolved with ethyl acetate, was washed in sequence with cooled 5% aqueous citric acid (3×100 ml), cooled 5% aqueous sodium bicarbonate and water, then concentrated and chromatographed on silica gel eluting with a mixture of methylene chloride and methanol (99:1 by volume) to give N-trityl-L-Phenylalanyl-L-leucylglycine ethyl ester (18 g, 30 mmol) that was converted into the corresponding acid 8a (17 g) by treatment in ethyl alchool 95% (400 ml) with 1N sodium hydroxide (30 ml) for two hours at room temperature.

Workup

  1. filtrationwas filtered
  2. customthe solvent was removed under reduced pressure
  3. dissolutionThe crude material, dissolved with ethyl acetate
  4. washwas washed in sequence
  5. temperaturewith cooled 5% aqueous citric acid (3×100 ml)
  6. temperaturecooled 5% aqueous sodium bicarbonate and water
  7. concentrationconcentrated
  8. customchromatographed on silica gel eluting with a mixture of methylene chloride and methanol (99:1 by volume)

Sources & evidence

ORD record
ord-cb9fb9944082457096d0f3c42671f4f3
Source dataset
uspto-grants-1996_11
Patent number
US05571785

Reaction notes

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