2-Dimethylaminopyridine → 17-Allyl-14-(tert-butyl-dimethyl-silanyloxy)-1-hydroxy-12-{2-[4-(7-(tert-butyl-dimethyl-silanyloxy-carbonyl)heptanoyl-oxy)-3-methoxy-cyclohexyl]-1-methyl-vinyl}-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-aza-tricyclo[22.3.1.04,9] octacos-18-ene-2,3,10,16-tetraone

HRID 2075623Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2075623
[CH2:1]([CH:4]1[CH:30]=[C:29]([CH3:31])[CH2:28][CH:27]([CH3:32])[CH2:26][CH:25]([O:33][CH3:34])[CH:24]2[O:35][C:20]([OH:39])([CH:21]([CH3:38])[CH2:22][CH:23]2[O:36][CH3:37])[C:19](=[O:40])[C:18](=[O:41])[N:17]2[CH:12]([CH2:13][CH2:14][CH2:15][CH2:16]2)[C:11](=[O:42])[O:10][CH:9]([C:43]([CH3:54])=[CH:44][CH:45]2[CH2:50][CH2:49][CH:48]([OH:51])[CH:47]([O:52][CH3:53])[CH2:46]2)[CH:8]([CH3:55])[CH:7]([O:56][Si:57]([C:60]([CH3:63])([CH3:62])[CH3:61])([CH3:59])[CH3:58])[CH2:6][C:5]1=[O:64])[CH:2]=[CH2:3].[C:65]([Si:69]([CH3:83])([CH3:82])[O:70][C:71](=[O:81])[CH2:72][CH2:73][CH2:74][CH2:75][CH2:76][CH2:77][C:78](O)=[O:79])([CH3:68])([CH3:67])[CH3:66].CN(C1C=CC=CN=1)C.Cl.CN(C)CCCN=C=NCC>C(OCC)(=O)C.O.C(Cl)Cl>[CH2:1]([CH:4]1[CH:30]=[C:29]([CH3:31])[CH2:28][CH:27]([CH3:32])[CH2:26][CH:25]([O:33][CH3:34])[CH:24]2[O:35][C:20]([OH:39])([CH:21]([CH3:38])[CH2:22][CH:23]2[O:36][CH3:37])[C:19](=[O:40])[C:18](=[O:41])[N:17]2[CH:12]([CH2:13][CH2:14][CH2:15][CH2:16]2)[C:11](=[O:42])[O:10][CH:9]([C:43]([CH3:54])=[CH:44][CH:45]2[CH2:50][CH2:49][CH:48]([O:51][C:78](=[O:79])[CH2:77][CH2:76][CH2:75][CH2:74][CH2:73][CH2:72][C:71]([O:70][Si:69]([C:65]([CH3:67])([CH3:66])[CH3:68])([CH3:82])[CH3:83])=[O:81])[CH:47]([O:52][CH3:53])[CH2:46]2)[CH:8]([CH3:55])[CH:7]([O:56][Si:57]([C:60]([CH3:61])([CH3:62])[CH3:63])([CH3:58])[CH3:59])[CH2:6][C:5]1=[O:64])[CH:2]=[CH2:3]

Komponenten

7

Edukt 4

HCID 218852-DimethylaminopyridineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 23080810O-mono(tert-butyl-dimethyl-silanyl)octanedioic acidHCID 7379247117-Allyl-14-(tert-butyl-dimethyl-silanyloxy)-1-hydroxy-12-[2-(4-hydroxy-3-methoxy-cyclohexyl)-1-methyl-vinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-aza-tricyclo[22.3.1.04,9]octacos-18-ene-2,3,10,16-tetraone

Produkt 1

HCID 8660279117-Allyl-14-(tert-butyl-dimethyl-silanyloxy)-1-hydroxy-12-{2-[4-(7-(tert-butyl-dimethyl-silanyloxy-carbonyl)heptanoyl-oxy)-3-methoxy-cyclohexyl]-1-methyl-vinyl}-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-aza-tricyclo[22.3.1.04,9] octacos-18-ene-2,3,10,16-tetraoneAusbeute 24,7 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6344DichloromethaneLösungsmittelHCID 22728543Water ethylacetateLösungsmittel

Versuchsvorschrift

A mixture of 17-allyl-14-(tert-butyl-dimethyl-silanyloxy)-1-hydroxy-12-[2-(4-hydroxy-3-methoxy-cyclohexyl)-1-methyl-vinyl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-aza-tricyclo[22.3.1.04,9]octacos-18-ene-2,3,10,16-tetraone (FK506; 138 mg, 0.15 mmol), O-mono(tert-butyl-dimethyl-silanyl)octanedioic acid (86.7 mg, 0.218 mmol), dimethylaminopyridine (DMAP; 16.5 mg, 0.098 mmol), 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (EDC/HCl; 69.1 mg, 0.261 mmol) and methylene chloride (CH2Cl2; 1 ml) was stirred at room temperature for 1.5 hours. The reaction product was poured over an ethyl acetate-water mixed fluid and extracted. The organic phase obtained was washed with water and brine, after which it was dried with magnesium sulfate (MgSO4). After the MgSO4 was separated by filtration, concentration under reduced pressure was conducted. The residue thus obtained was purified using a silica gel column (eluted with 20% AcOEt (in n-hexane)) to yield the desired 17-allyl-14-(tert-butyl-dimethyl-silanyloxy)-1-hydroxy-12-{2-[4-(7-(tert-butyl-dimethyl-silanyloxy-carbonyl)heptanoyl-oxy)-3-methoxy-cyclohexyl]-1-methyl-vinyl}-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-aza-tricyclo[22.3.1.04,9]octacos-18-ene-2,3,10,16-tetraone (44 mg, 24.6%).

Aufarbeitung

  1. extractionextracted
  2. customThe organic phase obtained
  3. washwas washed with water and brine
  4. dry with materialafter which it was dried with magnesium sulfate (MgSO4)
  5. customAfter the MgSO4 was separated by filtration, concentration under reduced pressure
  6. customThe residue thus obtained
  7. customwas purified
  8. washa silica gel column (eluted with 20% AcOEt (in n-hexane))

Quellen und Nachweise

ORD-Eintrag
ord-0337fe1caf394d339b21286d055d7a54
Quelldatensatz
uspto-grants-2011_04
Patentnummer
US07919653B2

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