4-Methylmorpholine → FMOC-Asp(OBzl)-Glu(O-tBu)-Tyr(Bzl)-OBzl

HRID 464552Notes

Reaction equation

HRID 464552 reaction equation
[NH:1]([C:17]([O:19][CH2:20][CH:21]1[C:33]2[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=2)[C:27]2[C:22]1=[CH:23][CH:24]=[CH:25][CH:26]=2)=[O:18])[C@H:2]([C:14](O)=[O:15])[CH2:3]C(=O)OCC1C=CC=CC=1.[CH2:34]([O:38][C:39](Cl)=[O:40])[CH:35]([CH3:37])[CH3:36].CN1CCOCC1.[NH:49](C(OCC1C2C(=CC=CC=2)C2C1=CC=CC=2)=O)[C@H:50]([C:60]([NH:62][C@H:63]([C:79]([O:81][CH2:82][C:83]1[CH:88]=[CH:87][CH:86]=[CH:85][CH:84]=1)=[O:80])[CH2:64][C:65]1[CH:70]=[CH:69][C:68]([O:71][CH2:72][C:73]2[CH:78]=[CH:77][CH:76]=[CH:75][CH:74]=2)=[CH:67][CH:66]=1)=[O:61])[CH2:51][CH2:52][C:53](=[O:59])[O:54][C:55]([CH3:58])([CH3:57])[CH3:56].N1CC[CH2:109][CH2:108][CH2:107]1>C(OCC)(=O)C.CN(C)C=O>[NH:1]([C:17]([O:19][CH2:20][CH:21]1[C:33]2[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=2)[C:27]2[C:22]1=[CH:23][CH:24]=[CH:25][CH:26]=2)=[O:18])[C@H:2]([C:14]([NH:49][C@H:50]([C:60]([NH:62][C@H:63]([C:79]([O:81][CH2:82][C:83]1[CH:84]=[CH:85][CH:86]=[CH:87][CH:88]=1)=[O:80])[CH2:64][C:65]1[CH:66]=[CH:67][C:68]([O:71][CH2:72][C:73]2[CH:78]=[CH:77][CH:76]=[CH:75][CH:74]=2)=[CH:69][CH:70]=1)=[O:61])[CH2:51][CH2:52][C:53](=[O:59])[O:54][C:55]([CH3:58])([CH3:56])[CH3:57])=[O:15])[CH2:3][C:39](=[O:40])[O:38][CH2:34][C:35]1[CH:37]=[CH:109][CH:108]=[CH:107][CH:36]=1

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 8082PiperidineHCID 62365Isobutyl chloroformateHCID 13534309FMOC-Glu(OtBu)-Tyr(Bzl)-OBzlHCID 13966931(2S)-4-(Benzyloxy)-2-({[(9H-fluoren-9-yl)methoxy]carbonyl}amino)-4-oxobutanoic acid

Product 1

HCID 13534311FMOC-Asp(OBzl)-Glu(O-tBu)-Tyr(Bzl)-OBzlYield 72%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-15 °C

Procedure

FMOC-Asp(OBzl) (4.45 g; 10 mmol) was dissolved in ethyl acetate (30 ml) and cooled down to -15° C. Isobutylchloroformate (1.5 ml; 11 mmol) was added to the solution, followed by N-methylmorpholine (1.2 ml; 11 mmol). FMOC-Glu(O-t-Bu)-Tyr(Bzl)-OBzl (29) (6 g; 7.8 mmol) was treated with 10% piperidine in dimethylformamide (100 ml) for 1 h. The solvent was removed under reduced pressure and the residue was dissolved in dimethylformamide (30 ml) and added to the first solution at -15° C. The reaction mixture was stirred overnight at ambient temperature. Solids were removed by filtration and under reduced pressure. The residue was dissolved in ethylacetate (150 ml) and the insoluble material was removed by filtration. The organic solution washed with 0.05N hydrochloric acid (3×40 ml), water (40 ml) and dried over anhydrous sodium sulfate. The drying agent was removed by filtration and the filtrate evaporated under reduced pressure. The residue was crystallized from ethylacetate/petroleum ether to give 5.5 g (72 percent) of 30, m.p. 96°-99° C.

Workup

  1. customThe solvent was removed under reduced pressure
  2. dissolutionthe residue was dissolved in dimethylformamide (30 ml)
  3. additionadded to the first solution at -15° C
  4. customSolids were removed by filtration and under reduced pressure
  5. dissolutionThe residue was dissolved in ethylacetate (150 ml)
  6. customthe insoluble material was removed by filtration
  7. washThe organic solution washed with 0.05N hydrochloric acid (3×40 ml), water (40 ml)
  8. dry with materialdried over anhydrous sodium sulfate
  9. customThe drying agent was removed by filtration
  10. customthe filtrate evaporated under reduced pressure
  11. customThe residue was crystallized from ethylacetate/petroleum ether

Sources & evidence

ORD record
ord-f585bddfd0df458a98c3ea66c1e91b91
Source dataset
uspto-grants-1985_10
Patent number
US04547489

Reaction notes

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