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Dicyclohexylcarbodiimide → 17-Allyl-12-(2-(4-((-)-2-trifluoromethyl-2-methoxy-2-phenylacetoxy)-3-methoxycyclohexyl)-1-methylvinyl)-1,14-dihydroxy-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo(22.3.1.04,9)octacos-18-ene-2, 3,10,16-tetraone

HRID 330048
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Reaktionsgleichung von HRID 330048
[F:1][C:2]([F:16])([F:15])[C:3]([O:13][CH3:14])([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[C:4]([OH:6])=[O:5].C1(N=C=NC2CCCCC2)CCCCC1.[CH3:32][C@H:33]1[CH2:64][C:63]([CH3:65])=[CH:62][C@@H:61]([CH2:66][CH:67]=[CH2:68])[C:59](=[O:60])[CH2:58][C@H:57]([OH:69])[C@@H:56]([CH3:70])[C@@H:55](/[C:71](/[CH3:82])=[CH:72]/[C@H:73]2[CH2:78][C@@H:77]([O:79][CH3:80])[C@H:76](O)[CH2:75][CH2:74]2)[O:54][C:52](=[O:53])[C@H:51]2[N:46]([CH2:47][CH2:48][CH2:49][CH2:50]2)[C:44](=[O:45])[C:42](=[O:43])[C@:40]2([OH:83])[O:41][C@@H:36]([C@@H:37]([O:85][CH3:86])[CH2:38][C@H:39]2[CH3:84])[C@@H:35]([O:87][CH3:88])[CH2:34]1>C(OCC)(=O)C.CN(C1C=CN=CC=1)C.C(OCC)C>[CH2:66]([CH:61]1[CH:62]=[C:63]([CH3:65])[CH2:64][CH:33]([CH3:32])[CH2:34][CH:35]([O:87][CH3:88])[CH:36]2[O:41][C:40]([OH:83])([CH:39]([CH3:84])[CH2:38][CH:37]2[O:85][CH3:86])[C:42](=[O:43])[C:44](=[O:45])[N:46]2[CH:51]([CH2:50][CH2:49][CH2:48][CH2:47]2)[C:52](=[O:53])[O:54][CH:55]([C:71]([CH3:82])=[CH:72][CH:73]2[CH2:74][CH2:75][CH:76]([O:5][C:4](=[O:6])[C:3]([C:2]([F:15])([F:16])[F:1])([O:13][CH3:14])[C:7]3[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=3)[CH:77]([O:79][CH3:80])[CH2:78]2)[CH:56]([CH3:70])[CH:57]([OH:69])[CH2:58][C:59]1=[O:60])[CH:67]=[CH2:68]
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Komponenten

7

Edukt 3

HCID 10868DicyclohexylcarbodiimideHCID 86531Mosher's acidHCID 445643Tacrolimus

Produkt 1

HCID 5722415617-Allyl-12-(2-(4-((-)-2-trifluoromethyl-2-methoxy-2-phenylacetoxy)-3-methoxycyclohexyl)-1-methylvinyl)-1,14-dihydroxy-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo(22.3.1.04,9)octacos-18-ene-2, 3,10,16-tetraone

Reagenzien, Katalysatoren, Lösungsmittel

3
HCID 142844-(Dimethylamino)pyridineKatalysatorHCID 3283Diethyl EtherLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

To a solution of (-)-2-trifluoromethyl-2-methoxy-2-phenylacetic acid (51 mg) in ethyl acetate (10 ml) was added at room temperature N,N'-dicyclohexylcarbodiimide (47 mg). After stirring for 1.5 hours at room temperature, then the FR-900506 substance (25.0 mg) and 4-(N,N-dimethylamino)-pyridine (11 mg) were added, followed by stirring at room temperature for 3.5 hours. The resulting solution was concentrated to provide a residue, which was taken up in diethyl ether and then washed successively with hydrochloric acid, an aqueous sodium hydrogen carbonate and an aqueous sodium chloride. The organic layer was dried over sodium sulfate and concentrated to provide a residue, which was chromatographed on silica gel (developing solvent: dichloromethane and diethyl ether, 10:1 v/v) to give 17-allyl-12-[2-[4-[(-)-2-trifluoromethyl-2-methoxy-2phenylacetoxy]-3-methoxycyclohexyl]-1-methylvinyl]-1,14-dihydroxy-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.04,9 ]octacos-18-ene-2,3,10,16-tetraone (6.5 mg) and 17-allyl-14-[(-)- 2-trifluoromethyl-2-methoxy-2-phenylacetoxy]-12-[2-[4-(-)-2-trifluoromethyl-2-methoxy-2-phenylacetoxy]-3-methoxycyclohexyl]3-methylvinyl]-1-hydroxy-23,25 -dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo-[22.3.1.04,9 octacos-18-ene-2,3,10,16-tetraone (20.2 mg).

Aufarbeitung

  1. stirringby stirring at room temperature for 3.5 hours
  2. concentrationThe resulting solution was concentrated
  3. customto provide a residue, which
  4. washwashed successively with hydrochloric acid
  5. dry with materialThe organic layer was dried over sodium sulfate
  6. concentrationconcentrated
  7. customto provide a residue, which
  8. customwas chromatographed on silica gel (developing solvent: dichloromethane and diethyl ether, 10:1 v/v)

Quellen und Nachweise

ORD-Eintrag
ord-a213700641a24844b64571256c1b0b5a
Quelldatensatz
uspto-grants-1990_01
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US04894366

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