4-Bromo-2-(((2-(5,5-dimethyl-1-cyclopenten-1-yl)-2'-fluoro-5'-(methyloxy)-1,1'-biphenyl-4-yl)methyl)oxy)pyridine → Ethyl 3-(2-(((2-(5,5-dimethyl-1-cyclopenten-1-yl)-2'-fluoro-5'-(methyloxy)-1,1'-biphenyl-4-yl)methyl)oxy)-4-pyridinyl)propanoate

HRID 1662575

Reaktionsgleichung

Reaktionsgleichung von HRID 1662575
Br[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][C:13]([C:16]3[CH:21]=[C:20]([O:22][CH3:23])[CH:19]=[CH:18][C:17]=3[F:24])=[C:12]([C:25]3[C:29]([CH3:31])([CH3:30])[CH2:28][CH2:27][CH:26]=3)[CH:11]=2)[CH:3]=1.[Br-].[CH2:33]([O:35][C:36](=[O:40])[CH2:37][CH2:38][Zn+])[CH3:34]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].CC(P(C(C)(C)C)[C]1[CH][CH][CH][CH]1)(C)C.C1C=CC([C]2[C](C3C=CC=CC=3)[C](C3C=CC=CC=3)[C](C3C=CC=CC=3)[C]2C2C=CC=CC=2)=CC=1.[Fe].C1COCC1>[CH3:30][C:29]1([CH3:31])[C:25]([C:12]2[CH:11]=[C:10]([CH2:9][O:8][C:4]3[CH:3]=[C:2]([CH2:38][CH2:37][C:36]([O:35][CH2:33][CH3:34])=[O:40])[CH:7]=[CH:6][N:5]=3)[CH:15]=[CH:14][C:13]=2[C:16]2[CH:21]=[C:20]([O:22][CH3:23])[CH:19]=[CH:18][C:17]=2[F:24])=[CH:26][CH2:27][CH2:28]1

Komponenten

6

Edukt 2

HCID 577058284-Bromo-2-(((2-(5,5-dimethyl-1-cyclopenten-1-yl)-2'-fluoro-5'-(methyloxy)-1,1'-biphenyl-4-yl)methyl)oxy)pyridineHCID 178471816HCID 178471816, Verbindung

Produkt 1

HCID 57706923Ethyl 3-(2-(((2-(5,5-dimethyl-1-cyclopenten-1-yl)-2'-fluoro-5'-(methyloxy)-1,1'-biphenyl-4-yl)methyl)oxy)-4-pyridinyl)propanoateAusbeute 78 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumKatalysatorHCID 178454872HCID 178454872, VerbindungKatalysatorHCID 8028TetrahydrofuranLösungsmittel2×

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

To a sealed tube containing 95.A (0.1059 g, 0.22 mmol), bis(dibenzylideneacetone)palladium (0.0068 g, 0.012 mmol), and CTC-Q-Phos (commercially available from Strem Chemicals) (0.0079 g, 0.011 mmol) was added dry THF (2.1 mL). After 5 minutes, 3-ethoxy-3-oxopropylzinc bromide, 0.5 M solution in THF (0.9 mL, 0.45 mmol) was added dropwise. After 1 hour, the mixture was heated to 80° C. and monitored with TLC and LC-MS. After 16.5 hours, the reaction was cooled to room temperature, and then the organic solvent was removed under reduced pressure. The solid was filtered off, and the solvent was concentrated. The residue was purified by silica gel flash chromatography (0-40% EtOAc/hexane) to afford 95.B (86.2 mg, 78% yield). 1H NMR (500 MHz) (CDCl3) δ ppm 8.10 (1H, d, J=5.4 Hz), 7.41 (1H, dd, J=7.9, 1.8 Hz), 7.33 (2H, dd, J=4.6, 1.5 Hz), 6.98 (1H, m), 6.81 (3H, m), 6.70 (1H, s), 5.52 (1H, t, J=2.0 Hz), 5.42 (2H, s), 4.15 (2H, q, J=7.1 Hz), 3.76 (3H, s), 2.93 (2H, t, J=7.7 Hz), 2.66 (2H, m), 2.25 (2H, td, J=7.0, 2.4 Hz), 1.66 (2H, t, J=7.0 Hz), 1.25 (3H, t, J=7.1 Hz), 0.86 (6H, s).

Aufarbeitung

  1. waitAfter 1 hour
  2. waitAfter 16.5 hours
  3. temperaturethe reaction was cooled to room temperature
  4. customthe organic solvent was removed under reduced pressure
  5. filtrationThe solid was filtered off
  6. concentrationthe solvent was concentrated
  7. customThe residue was purified by silica gel flash chromatography (0-40% EtOAc/hexane)

Quellen und Nachweise

ORD-Eintrag
ord-c13e7fedcd5e494f9192825e06edb868
Quelldatensatz
uspto-grants-2011_10
Patentnummer
US08030354B2

Verknüpfte Notizen

Wird geladen…