Ethylmorpholine → Boc-Tyr-(D)Ala-Gly-MePhe methioninol

HRID 1903872Notes

Reaction equation

HRID 1903872 reaction equation
[NH:1]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[C@H:2]([C:11]([NH:13][C@@H:14]([C:16]([NH:18][CH2:19][C:20](O)=[O:21])=[O:17])[CH3:15])=[O:12])[CH2:3][C:4]1[CH:9]=[CH:8][C:7]([OH:10])=[CH:6][CH:5]=1.C(N1CCOCC1)C.C(OC(Cl)=O)C(C)C.[NH:46]([CH3:58])[C@H:47]([C:55]([OH:57])=[O:56])[CH2:48][C:49]1[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=1.[NH2:59][C@H:60]([CH2:65][OH:66])[CH2:61][CH2:62][S:63][CH3:64]>C1COCC1.N[C@H](C(N[C@@H](C(NCC(N[C@H](C(O)=O)CC1C=CC=CC=1)=O)=O)C)=O)CC1C=CC(O)=CC=1.N[C@H](CO)CCSC.C(O)(=O)C>[NH:1]([C:23]([O:25][C:26]([CH3:27])([CH3:29])[CH3:28])=[O:24])[C@H:2]([C:11]([NH:13][C@@H:14]([C:16]([NH:18][CH2:19][C:20]([N:46]([CH3:58])[C@H:47]([C:55]([OH:57])=[O:56])[CH2:48][C:49]1[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=1)=[O:21])=[O:17])[CH3:15])=[O:12])[CH2:3][C:4]1[CH:5]=[CH:6][C:7]([OH:10])=[CH:8][CH:9]=1.[NH2:59][C@H:60]([CH2:65][OH:66])[CH2:61][CH2:62][S:63][CH3:64]

Participants

8

Reactant 4

HCID 7525Ethylmorpholine2×HCID 62365Isobutyl chloroformateHCID 7272028Boc-tyr-D-ala-gly-OHHCID 131713440H-MePhe methioninol

Product 1

HCID 131712177Boc-Tyr-(D)Ala-Gly-MePhe methioninol

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 8028TetrahydrofuranSolventHCID 131712171H-Tyr-(D)Ala-Gly-Phe methioninolSolvent2×

Procedure

1.23 g of Boc-Tyr-(D)Ala-Gly-OH is dissolved in 30 ml of THF and cooled to 15°. 0.38 ml of ethylmorpholine are added with stirring followed by 0.39 ml of chloroformic acid iso-butyl ester and stirring continued for 10 minutes. A cold solution of 14 g of TFA.H-MePhe-methioninol and 0.45 ml of N-ethylmorpholine in 12 ml of TFA are added with stirring at -15°. The mixture is stirred for 20 hours at 0°, diluted with 250 ml of acetic acid and washed repeatedly with water, 1 N citric acid, 10% KHCO3 and 30% NaCl solution. The liquid is dried over Na2SO4 and evaporated. The residue is purified chromatographically on kieselgel using a mixture of methanol/CH2Cl2 /50% acetic acid, whereby the title compound is obtained. Decomp. 160°.

Workup

  1. temperaturecooled to 15°
  2. stirringstirring
  3. stirringwith stirring at -15°
  4. stirringThe mixture is stirred for 20 hours at 0°
  5. washwashed repeatedly with water, 1 N citric acid, 10% KHCO3 and 30% NaCl solution
  6. dry with materialThe liquid is dried over Na2SO4
  7. customevaporated
  8. customThe residue is purified chromatographically on kieselgel
  9. additiona mixture of methanol/CH2Cl2 /50% acetic acid, whereby the title compound
  10. customis obtained
  11. custom160°

Sources & evidence

ORD record
ord-56049c7444b54325a9f1bc890210a4f4
Source dataset
uspto-grants-1984_03
Patent number
US04438103

Reaction notes

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