4-Methylmorpholine → HCID 53656047, compound

HRID 462869Notes

Reaction equation

HRID 462869 reaction equation
[NH:1](C(OCC1C=CC=CC=1)=O)[C@H:2]([C:11]([NH:13][C@H:14]([C:16]([O:18]CC1C=CC=CC=1)=[O:17])[CH3:15])=[O:12])[CH2:3][C:4](=[O:10])[O:5]C(C)(C)C.S(O)(C1C=[CH:44][C:42]([CH3:43])=[CH:41]C=1)(=O)=O.O.CN1CCOCC1.[NH:55]([C:73]([O:75][CH2:76][C:77]1[CH:82]=[CH:81][CH:80]=[CH:79][CH:78]=1)=[O:74])[C@H:56]([C:63]([O:65]N1C(=O)CCC1=O)=O)[CH2:57][O:58][C:59]([CH3:62])([CH3:61])[CH3:60].C(N(CC)CCN)C>CN(C=O)C.[Pd]>[CH2:76]([O:75][C:73]([NH:55][C@H:56]([C:63]([NH:1][C@H:2]([C:11]([NH:13][C@H:14]([C:16]([OH:18])=[O:17])[CH3:15])=[O:12])[CH:3]([C:42]([CH3:44])([CH3:43])[CH3:41])[C:4](=[O:10])[OH:5])=[O:65])[CH2:57][O:58][C:59]([CH3:60])([CH3:61])[CH3:62])=[O:74])[C:77]1[CH:78]=[CH:79][CH:80]=[CH:81][CH:82]=1

Participants

8

Reactant 5

HCID 79724-Methylmorpholine2×HCID 60993N,N-DiethylethylenediamineHCID 521998p-Toluenesulfonic acid monohydrateHCID 13501986HCID 13501986, compoundHCID 138199212,5-Dioxopyrrolidin-1-yl N-[(benzyloxy)carbonyl]-O-tert-butyl-L-serinate

Product 1

HCID 53656047HCID 53656047, compound

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 6228DimethylformamideSolvent

Procedure

Z-Asp(OtBu)-Ala-OBzl (43.6 g, 90 mmol) was dissolved in 1 liter DMF and hydrogenated in the presence of Tos-OH.H2O (17.1 g, 90 mmol) and 10% Pd-C. After the hydrogenation was completed the catalyst was filtered off. The filtrate was cooled to 0°, neutralized with N-methylmorpholine (9.9 ml, 90 mmol) and added to Z-Ser(tBu)-OSu. Another portion of N-methylmorpholine (9.9 ml, 90 mmol) was added and the reaction mixture was stirred at 0° for 1 h and at 25° for 18 h. 2-Diethylamino-ethylamine (2.83 ml, 20 mmol) was added to the reaction mixture and stirring was continued for 4 h. The solution was evaporated in vacuo, the residue dissolved in 0.5N NaOH (0.5 l) and extracted with ether (3×0.2 l). To the alkaline phase 0.4 l ethyl acetate was added and acidified with 5% KHSO4 /10% K2SO4 -solution. The acidic layer was again extracted with ethyl acetate (2×0.3 l). The combined organic layers were washed with 5% KHSO4 /10% K2SO4 -sol. (1×0.3 l) and saturated NaCl-sol., dried over Na2SO4, filtered and evaporated in vacuo.

Workup

  1. filtrationwas filtered off
  2. temperatureThe filtrate was cooled to 0°
  3. stirringstirring
  4. waitwas continued for 4 h
  5. customThe solution was evaporated in vacuo
  6. dissolutionthe residue dissolved in 0.5N NaOH (0.5 l)
  7. extractionextracted with ether (3×0.2 l)
  8. additionTo the alkaline phase 0.4 l ethyl acetate was added
  9. extractionThe acidic layer was again extracted with ethyl acetate (2×0.3 l)
  10. washThe combined organic layers were washed with 5% KHSO4 /10% K2SO4 -sol
  11. dry with material, dried over Na2SO4
  12. filtrationfiltered
  13. customevaporated in vacuo

Sources & evidence

ORD record
ord-8c581baba7244a5392a89e2e9aa483c1
Source dataset
uspto-grants-1985_05
Patent number
US04517119

Reaction notes

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