4-Methylmorpholine → Boc-(D)Phe-Pro-OBzl

HRID 4980

Reaktionsgleichung

Reaktionsgleichung von HRID 4980
[NH:1]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[C@@H:2]([C:10]([OH:12])=O)[CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.CN1CCOCC1.ClC(OCC(C)C)=O.[NH:35]1[CH2:49][CH2:48][CH2:47][C@H:36]1[C:37]([O:39][CH2:40][C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1)=[O:38].Cl.C(N(CC)CC)C>C1COCC1.C(Cl)(Cl)Cl>[NH:1]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[C@@H:2]([C:10]([N:35]1[CH2:49][CH2:48][CH2:47][C@H:36]1[C:37]([O:39][CH2:40][C:41]1[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=1)=[O:38])=[O:12])[CH2:3][C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1

Komponenten

8

Edukt 5

HCID 79724-MethylmorpholineHCID 8471TriethylamineHCID 62365Isobutyl chloroformateHCID 637610Boc-D-phenylalanineHCID 2733413Proline benzyl ester hydrochloride

Produkt 1

HCID 11155205Boc-(D)Phe-Pro-OBzlAusbeute 89,1 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6212ChloroformLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

Boc-(D)Phe-Pro-OH was produced by first preparing the dipeptide benzyl ester and then removing the ester by catalytic hydrogenation. Boc-(D)Phe-OH (10.0 g, 37.7 mmoles) was dissolved in 50 mL of THF and N-methylmorpholine (4.14 mL, 37.7 mmoles) was added. The solution was cooled to -20° and isobutyl chloroformate (4.90 mL, 37.7 mmoles) was added. After 5 min, H-Pro-OBzl.HCl (9.11 g, 37.7 mmoles), dissolved in 50 mL of chloroform and cooled to -20°, was added. Triethylamine (5.25 mL, 37.7 mmoles) was added and the mixture was stirred for 1 h at -20° and 2 h at room temperature. The reaction mixture was filtered and the filtrate evaporated. The residue was dissolved in ethyl acetate and was washed with 0.2N hydrochloric acid, 5% aqueous sodium bicarbonate, and saturated aqueous sodium chloride. The organic phase was dried over anhydrous sodium sulfate, filtered, and evaporated to yield 15.2 g of Boc-(D)Phe-Pro-OBzl as an oil. The benzyl ester (15.2 g) was dissolved in 100 mL of methanol and it was hydrogenated at an initial pressure of 40 psi on a Parr apparatus in the presence of 0.5 g of 10% Pd/C. The reaction solution was filtered through Celite™ and evaporated to yield a solid. This solid material was isolated and was washed with ethyl acetate and then by ether to yield 10.0 g of the desired product (mp 176.5°-177°).

Aufarbeitung

  1. customremoving the ester by catalytic hydrogenation
  2. temperatureThe solution was cooled to -20°
  3. temperaturecooled to -20°
  4. additionwas added
  5. filtrationThe reaction mixture was filtered
  6. customthe filtrate evaporated
  7. dissolutionThe residue was dissolved in ethyl acetate
  8. washwas washed with 0.2N hydrochloric acid, 5% aqueous sodium bicarbonate, and saturated aqueous sodium chloride
  9. dry with materialThe organic phase was dried over anhydrous sodium sulfate
  10. filtrationfiltered
  11. customevaporated

Quellen und Nachweise

ORD-Eintrag
ord-3709ccfe828b4265b38b3fb14b3078b9
Quelldatensatz
uspto-grants-1993_09
Patentnummer
US05242904

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