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Triphenylphosphine → Methyl [2-fluoro-4-(2-{(1S,2R)-2-[1-(5-methoxypyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethoxy)phenyl]acetate

HRID 1474693
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 1474693
[CH3:1][O:2][C:3]1[CH:4]=[N:5][C:6]([N:9]2[CH2:14][CH2:13][CH:12]([C@H:15]3[CH2:17][C@H:16]3[CH2:18][CH2:19][OH:20])[CH2:11][CH2:10]2)=[N:7][CH:8]=1.[F:21][C:22]1[CH:27]=[C:26](O)[CH:25]=[CH:24][C:23]=1[CH2:29][C:30]([O:32][CH3:33])=[O:31].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>ClCCl>[F:21][C:22]1[CH:27]=[C:26]([O:20][CH2:19][CH2:18][C@@H:16]2[CH2:17][C@@H:15]2[CH:12]2[CH2:13][CH2:14][N:9]([C:6]3[N:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][N:5]=3)[CH2:10][CH2:11]2)[CH:25]=[CH:24][C:23]=1[CH2:29][C:30]([O:32][CH3:33])=[O:31]
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Komponenten

6

Edukt 4

HCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 58415153Methyl 2-(2-Fluoro-4-hydroxyphenyl)acetateHCID 89581860HCID 89581860, Verbindung

Produkt 1

HCID 89583879Methyl [2-fluoro-4-(2-{(1S,2R)-2-[1-(5-methoxypyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethoxy)phenyl]acetate

Reagenzien, Katalysatoren, Lösungsmittel

1
HCID 6344DichloromethaneLösungsmittel2×

Versuchsvorschrift

2-{(1S,2R)-2-[1-(5-Methoxypyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethanol (1.2 g, 4.33 mmol), methyl 2-(2-fluoro-4-hydroxyphenyl)acetate (0.956 g, 5.19 mmol) and triphenylphosphine (1.702 g, 6.49 mmol) were dissolved in dichloromethane (20 ml). The mixture was stirred at RT under N2 for 5 min and diisopropyl azodicarboxylate (1.274 ml, 6.49 mmol) was added. The mixture was stirred at RT overnight. The mixture was diluted with DCM (50 ml), washed with water, dried and evaporated. The crude material was purified by column chromatography on silica gel (50 g SNAP, 5˜30% EtOAc in hexane) to afford the desired product which contains some impurities. This material was re-purified by column chromatography on silica gel (50 g SNAP, 2˜5% EtOAc in DCM) to afford the title compound. LC/MS (m/z): 444 (M+H)+. Rf was 0.4 @ 30% EtOAc in hexanes (blue spot on CAM stain).

Aufarbeitung

  1. stirringThe mixture was stirred at RT overnight
  2. washwashed with water
  3. customdried
  4. customevaporated
  5. customThe crude material was purified by column chromatography on silica gel (50 g SNAP, 5˜30% EtOAc in hexane)

Quellen und Nachweise

ORD-Eintrag
ord-35d26808f35c4b42963b27b1f313184b
Quelldatensatz
uspto-grants-2015_04
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US09018224B2

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