Tributylphosphine → 6-[3-(4-Acetyl-3-hydroxy-2-propyl-phenoxymethyl)-phenoxy]-nicotinonitrile

HRID 2266990

Reaktionsgleichung

Reaktionsgleichung von HRID 2266990
[OH:1][CH2:2][C:3]1[CH:4]=[C:5]([CH:15]=[CH:16][CH:17]=1)[O:6][C:7]1[CH:14]=[CH:13][C:10]([C:11]#[N:12])=[CH:9][N:8]=1.[OH:18][C:19]1[C:24]([CH2:25][CH2:26][CH3:27])=[C:23](O)[CH:22]=[CH:21][C:20]=1[C:29](=[O:31])[CH3:30].C(P(CCCC)CCCC)CCC.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O>C(OCC)C.C1(C)C=CC=CC=1.ClCCl>[C:29]([C:20]1[CH:21]=[CH:22][C:23]([O:1][CH2:2][C:3]2[CH:4]=[C:5]([CH:15]=[CH:16][CH:17]=2)[O:6][C:7]2[CH:14]=[CH:13][C:10]([C:11]#[N:12])=[CH:9][N:8]=2)=[C:24]([CH2:25][CH2:26][CH3:27])[C:19]=1[OH:18])(=[O:31])[CH3:30]

Komponenten

7

Edukt 4

HCID 13831TributylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 27751982',4'-Dihydroxy-3'-propylacetophenoneHCID 616796946-(3-Hydroxymethyl-phenoxy)-nicotinonitrile

Produkt 1

HCID 685352096-[3-(4-Acetyl-3-hydroxy-2-propyl-phenoxymethyl)-phenoxy]-nicotinonitrileAusbeute 33,1 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 3283Diethyl EtherLösungsmittelHCID 21877217Toluene methylene chlorideLösungsmittel

Reaktionsbedingungen

Temperatur
-20 °C

Versuchsvorschrift

Mix 6-(3-hydroxymethyl-phenoxy)-nicotinonitrile (1.63 g, 7.18 mmol) and 1-(2,4-dihydroxy-3-propyl-phenyl)-ethanone (1.33 g, 6.84 mmol) in 2:1 toluene/dichloromethane (24 mL). Cool to −20° C. and add tributylphosphine (2.6 mL, 10.26 mmol) dropwise. After stirring for 5 minutes, add 1,1′-(azodicarbonyl)dipiperidine in three batches. Allow the reaction mixture to warm to ambient temperature overnight. Concentrate under reduced pressure to give a yellow solid. Dilute with diethyl ether (50 mL) and cool to 0° C. Filter the white precipitate and concentrate the filtrate under reduced pressure to give a residue. Purification by flash chromatography, using 5% ethyl acetate/hexanes to 30% ethyl acetate/hexanes as a gradient eluent yields the title compound (0.91 g, 33%): MS (m/z): 401.2 (M−1). 1H NMR (CDCl3) 12.78 (s, 1H), 8.50 (s, 1H), 7.97 (dd, J=2.2 Hz, 8.8 Hz, 1H), 7.62 (d, J=8.8 Hz, 1H), 7.51 (t, J=8.0 Hz, 1H), 7.36 (d, J=7.8 Hz, 1H), 7.25 (s, 1H), 7.16 (d, J=8.0 Hz, 1H), 7.09 (d, J=8.8 Hz, 1H), 6.51 (d, J=8.8 Hz, 1H), 5.22 (s, 2H), 2.72 (t, J=7.6 Hz, 2H), 2.60 (s, 3H), 1.62-1.53 (m, 2H), 0.94 (t, J=7.6 Hz, 3H).

Aufarbeitung

  1. temperatureAllow the reaction mixture to warm to ambient temperature overnight
  2. concentrationConcentrate under reduced pressure
  3. customto give a yellow solid
  4. temperaturecool to 0° C
  5. filtrationFilter the white precipitate
  6. concentrationconcentrate the filtrate under reduced pressure
  7. customto give a residue
  8. customPurification by flash chromatography

Quellen und Nachweise

ORD-Eintrag
ord-cdd4e9418b27432088fea48359fed33d
Quelldatensatz
uspto-grants-2010_12
Patentnummer
US07858646B2

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