Triphenylphosphine → 3-[(R)-1-(5-Fluoro-2-methoxy-phenyl)-ethoxy]-2-nitro-pyridine

HRID 1406271

Reaktionsgleichung

Reaktionsgleichung von HRID 1406271
[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:11][CH3:12])=[C:6]([C@@H:8]([OH:10])[CH3:9])[CH:7]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O[C:33]1[C:34]([N+:39]([O-:41])=[O:40])=[N:35][CH:36]=[CH:37][CH:38]=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>C(=O)=O.C1(C)C=CC=CC=1.C(OCC)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:11][CH3:12])=[C:6]([C@H:8]([O:10][C:33]2[C:34]([N+:39]([O-:41])=[O:40])=[N:35][CH:36]=[CH:37][CH:38]=2)[CH3:9])[CH:7]=1

Komponenten

8

Edukt 4

HCID 11776TriphenylphosphineHCID 270573-Hydroxy-2-nitropyridineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 14928684(S)-1-(5-Fluoro-2-methoxyphenyl)ethan-1-ol

Produkt 1

HCID 674673633-[(R)-1-(5-Fluoro-2-methoxy-phenyl)-ethoxy]-2-nitro-pyridineAusbeute 86 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 280Carbon DioxideLösungsmittelHCID 1140TolueneLösungsmittel2×HCID 3283Diethyl EtherLösungsmittel

Versuchsvorschrift

To an ice cooled solution (0° C.) of (S)-1-(5-fluoro-2-methoxy-phenyl)-ethanol (see H. C. Brown, Tet. Letts., 35 (14), 2141-4, 1994. Optical purity of alcohol: >99.5% e.e. (based on SFC on a chiral column: Chiralpak IA (250*4.6 mm i.d.), eluent 5% methanol alcohol in carbon dioxide, Flow rate 4 mL/min, temp. 40° C., back pressure 150 bar, Rt=2.16 min (opposite enantiomer Rt=2.35 min))) (2.00 g, 11.7 mmol), triphenylphosphine (3.54 g, 13.5 mmol, 1.15 eq.) and 3-hydroxy-2-nitro-pyridine (1.81 g, 12.9 mmol, 1.1 eq) in toluene (100 mL) was added a solution of diisopropyl azodicarboxylate (2.73 g, 13.5 mmol, 1.15 eq.) in toluene (20 mL) at such a rate as to maintain the temperature below 10° C. The resulting mixture was stirred at room temperature for 18 hr. The crude reaction mixture was extracted with aqueous potassium hydroxide solution (2M, 2×50 mL). The organic phase was washed with brine and dried over magnesium sulphate before filtering. The filtrate was evaporated under reduced pressure to give an orange semi solid material. This material was suspended in diethyl ether and heptane (80:20 by volume) and filtered. This filtrate was evaporated under reduced pressure. The residue was purified by chromatography on silica gel eluting with a gradient of diethyl ether in heptane (50:50 to 80:20 by volume) to produce the title compound as a pale yellow oil (3.48 g, 86%).

Aufarbeitung

  1. temperatureto maintain the temperature below 10° C
  2. customThe crude reaction mixture
  3. extractionwas extracted with aqueous potassium hydroxide solution (2M, 2×50 mL)
  4. washThe organic phase was washed with brine
  5. dry with materialdried over magnesium sulphate
  6. filtrationbefore filtering
  7. customThe filtrate was evaporated under reduced pressure
  8. customto give an orange semi solid material
  9. filtrationheptane (80:20 by volume) and filtered
  10. customThis filtrate was evaporated under reduced pressure
  11. customThe residue was purified by chromatography on silica gel eluting with a gradient of diethyl ether in heptane (50:50 to 80:20 by volume)

Quellen und Nachweise

ORD-Eintrag
ord-bf48b5681496457a90bcb41a504aaf0d
Quelldatensatz
uspto-grants-2014_12
Patentnummer
US08916593B2

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