(8S,11R,15R)-11-(((9H-fluoren-9-yl)methoxy)carbonylamino)-8-ethyl-2,2-dimethyl-4,10-dioxo-3,6-dioxa-13-thia-9-azahexadecane-15,16-diyl didodecanoate → (5S,8R,12R)-8-amino-12-(dodecanoyloxy)-5-ethyl-7,15-dioxo-3,14-dioxa-10-thia-6-azahexacosan-1-oic acid

HRID 2204989Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2204989
[C:1]([O:14][C@H:15]([CH2:54][O:55][C:56](=[O:68])[CH2:57][CH2:58][CH2:59][CH2:60][CH2:61][CH2:62][CH2:63][CH2:64][CH2:65][CH2:66][CH3:67])[CH2:16][S:17][CH2:18][C@H:19]([NH:36]C(OCC1C2C=CC=CC=2C2C1=CC=CC=2)=O)[C:20](=[O:35])[NH:21][C@@H:22]([CH2:33][CH3:34])[CH2:23][O:24][CH2:25][C:26](=[O:32])[O:27]C(C)(C)C)(=[O:13])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12]>C(O)(C(F)(F)F)=O.C(Cl)Cl>[NH2:36][C@@H:19]([CH2:18][S:17][CH2:16][C@H:15]([O:14][C:1](=[O:13])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12])[CH2:54][O:55][C:56](=[O:68])[CH2:57][CH2:58][CH2:59][CH2:60][CH2:61][CH2:62][CH2:63][CH2:64][CH2:65][CH2:66][CH3:67])[C:20](=[O:35])[NH:21][C@@H:22]([CH2:33][CH3:34])[CH2:23][O:24][CH2:25][C:26]([OH:32])=[O:27]

Komponenten

4

Edukt 1

HCID 86678282(8S,11R,15R)-11-(((9H-fluoren-9-yl)methoxy)carbonylamino)-8-ethyl-2,2-dimethyl-4,10-dioxo-3,6-dioxa-13-thia-9-azahexadecane-15,16-diyl didodecanoate

Produkt 1

HCID 53476317(5S,8R,12R)-8-amino-12-(dodecanoyloxy)-5-ethyl-7,15-dioxo-3,14-dioxa-10-thia-6-azahexacosan-1-oic acid

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6344DichloromethaneLösungsmittelHCID 6422Trifluoroacetic acidLösungsmittel

Versuchsvorschrift

A solution of (8S,11R,15R)-11-(((9H-fluoren-9-yl)methoxy)carbonylamino)-8-ethyl-2,2-dimethyl-4,10-dioxo-3,6-dioxa-13-thia-9-azahexadecane-15,16-diyl didodecanoate (1 eq, from the previous step) in 50% TFA in DCM (0.05 M) was stirred in open air at 40° C. for 1.5 hours. The mixture was dried under a stream of air and briefly evaporated under high vacuum. The resulting oil was dissolved in 20% piperidine in THF (0.1 mL) and stirred at room temperature for 1 hour. The reaction mixture was diluted with ethyl acetate. The reaction mixture was concentrated en vaccuo. The crude mixture was purified by flash chromatography on a COMBIFLASH® system (ISCO) using a gradient of 0-10% methanol in DCM to give the product as a solid. 1H NMR (DMSO-d6): δ 8.30 (d, 1H), 5.11 (m, 1H), 4.27 (dd, 1H), 4.09 (dd, 1H), 3.96 (s, 2H), 3.67-3.76 (m, 2H), 3.37-3.48 (m, 2H), 2.71-2.95 (m, 4H), 2.25-2.28 (m, 4H), 1.23-1.62 (m, 41H), 0.83-0.88 (m, 6H). LRMS [M+H]=689.4.

Aufarbeitung

  1. customThe mixture was dried under a stream of air
  2. custombriefly evaporated under high vacuum
  3. dissolutionThe resulting oil was dissolved in 20% piperidine in THF (0.1 mL)
  4. additionThe reaction mixture was diluted with ethyl acetate
  5. concentrationThe reaction mixture was concentrated en vaccuo
  6. customThe crude mixture was purified by flash chromatography on a COMBIFLASH® system (ISCO)

Quellen und Nachweise

ORD-Eintrag
ord-2e9d99cd5dc54291aa516e644dc43eb2
Quelldatensatz
uspto-grants-2016_06
Patentnummer
US09365506B2

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