Citric Acid → Z-Thr(tBu)-Tyr(tBu)-Thr(tBu)-Gln-Asp(OtBu)-Phe-OCH3

HRID 971545Notes

Reaction equation

HRID 971545 reaction equation
[NH:1]([C:13]([O:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=[O:14])[C@H:2]([C:10]([OH:12])=O)[C@@H:3]([CH3:9])[O:4][C:5]([CH3:8])([CH3:7])[CH3:6].[CH3:23]CCCC(F)(F)C(O)CC[C@@H]1[C@@H](CCCCCCC(O)=O)C(=O)C[C@H]1O.C1CCC(NC2CCCCC2)CC1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O.[NH2:76][C@H:77]([C:90]([NH:92][C@H:93]([C:101]([NH:103][C@H:104]([C:110]([NH:112][C@H:113]([C:122]([NH:124][C@H:125]([C:133]([OH:135])=[O:134])[CH2:126][C:127]1[CH:132]=[CH:131][CH:130]=[CH:129][CH:128]=1)=[O:123])[CH2:114][C:115](=[O:121])[O:116][C:117]([CH3:120])([CH3:119])[CH3:118])=[O:111])[CH2:105][CH2:106][C:107](=[O:109])[NH2:108])=[O:102])[C@@H:94]([CH3:100])[O:95][C:96]([CH3:99])([CH3:98])[CH3:97])=[O:91])[CH2:78][C:79]1[CH:84]=[CH:83][C:82]([O:85][C:86]([CH3:89])([CH3:88])[CH3:87])=[CH:81][CH:80]=1>C(OCC)(=O)C.C(#N)C>[NH:1]([C:13]([O:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=[O:14])[C@H:2]([C:10]([NH:76][C@H:77]([C:90]([NH:92][C@H:93]([C:101]([NH:103][C@H:104]([C:110]([NH:112][C@H:113]([C:122]([NH:124][C@H:125]([C:133]([O:135][CH3:23])=[O:134])[CH2:126][C:127]1[CH:132]=[CH:131][CH:130]=[CH:129][CH:128]=1)=[O:123])[CH2:114][C:115](=[O:121])[O:116][C:117]([CH3:118])([CH3:119])[CH3:120])=[O:111])[CH2:105][CH2:106][C:107](=[O:109])[NH2:108])=[O:102])[C@@H:94]([CH3:100])[O:95][C:96]([CH3:97])([CH3:98])[CH3:99])=[O:91])[CH2:78][C:79]1[CH:80]=[CH:81][C:82]([O:85][C:86]([CH3:87])([CH3:88])[CH3:89])=[CH:83][CH:84]=1)=[O:12])[C@@H:3]([CH3:9])[O:4][C:5]([CH3:6])([CH3:7])[CH3:8]

Participants

7

Reactant 4

HCID 311Citric AcidHCID 7018812(2S,3R)-2-(((Benzyloxy)carbonyl)amino)-3-(tert-butoxy)butanoic acid2×HCID 7174909515-Hydroxy Lubiprostone Dicyclohexylammonium SaltHCID 131711567H-Tyr(tBu)-Thr(tBu)-Gln-Asp(OtBu)-Phe

Product 1

HCID 131711566Z-Thr(tBu)-Tyr(tBu)-Thr(tBu)-Gln-Asp(OtBu)-Phe-OCH3

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

The acid is liberated from 2.85 g of Z-Thr(tBu)-OH.dicyclohexylammonium salt in ethyl acetate by means of citric acid as described under 23 and the resulting oil consisting of Z-Thr(tBu)-OH is stirred with 3.33 g of H-Tyr(tBu)-Thr(tBu)-Gln-Asp(OtBu)-Phe-OCH 3 in 80 ml of acetonitrile at room temperature. 1.20 g of dicyclohexylcarbodiimde are added thereto in the solid form and the mixture is stirred for 23 hours at room temperature. After filtering off the precipitated dicyclohexylurea, which is washed with three portions of acetonitrile each of 7 ml, the solution is evaporated in vacuo and the residue is three times precipitated from ethyl acetate/alcohol solution by means of petroleum ether.

Workup

  1. addition1.20 g of dicyclohexylcarbodiimde are added
  2. filtrationAfter filtering off the precipitated dicyclohexylurea, which
  3. washis washed with three portions of acetonitrile each of 7 ml
  4. customthe solution is evaporated in vacuo
  5. customprecipitated from ethyl acetate/alcohol solution by means of petroleum ether

Sources & evidence

ORD record
ord-180f94b7c41c4d3ca34899414c115989
Source dataset
uspto-grants-1979_07
Patent number
US04159981

Reaction notes

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