Sodium hydride → 4-(2-Cyano-5-(3-pyridylmethoxy)phenoxy)-4-(2-methylphenyl)butanoic acid

HRID 322890

Reaktionsgleichung

Reaktionsgleichung von HRID 322890
[OH:1][CH:2]([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[CH3:14])[CH2:3][CH2:4][C:5]([O-:7])=[O:6].[Na+].[H-].[Na+].F[C:19]1[CH:26]=[C:25]([O:27][CH2:28][C:29]2[CH:30]=[N:31][CH:32]=[CH:33][CH:34]=2)[CH:24]=[CH:23][C:20]=1[C:21]#[N:22]>O1CCCC1>[C:21]([C:20]1[CH:23]=[CH:24][C:25]([O:27][CH2:28][C:29]2[CH:30]=[N:31][CH:32]=[CH:33][CH:34]=2)=[CH:26][C:19]=1[O:1][CH:2]([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[CH3:14])[CH2:3][CH2:4][C:5]([OH:7])=[O:6])#[N:22]

Komponenten

5

Edukt 3

HCID 24758Sodium hydrideHCID 220104982-Fluoro-4-(3-pyridylmethoxy)benzonitrileHCID 23665160HCID 23665160, Verbindung

Produkt 1

HCID 220101494-(2-Cyano-5-(3-pyridylmethoxy)phenoxy)-4-(2-methylphenyl)butanoic acid

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

A mixture of sodium 4-hydroxy-4-(2-methyl-phenyl)butanoate, thought to be the (R)-enantiomer, (3 g) and sodium hydride (1.5 g; 60% w/v dispersion in mineral oil; 37.5 mmol) in tetrahydrofuran (50 mL) is stirred at ambient temperature for 1 hour under an atmosphere of argon and is then warmed to 55° C. It is then treated with 2-fluoro-4-(3-pyridyl-methoxy)benzonitrile (3 g), in one portion, and stirring is continued at 55° C. for 15 hours. The reaction mixture is then cooled, concentrated in vacuo, and diluted with water (100 mL). The pH of the mixture is adjusted to 5 by treatment with concentrated hydrochloric acid and is then extracted with ethyl acetate (4×100 mL). The combined extracts are dried over magnesium sulphate and concentrated in vacuo, to give an oily residue. This residue is recrystallized from isopropyl ether to give 4-[2-cyano-5-(3-pyridylmethoxy)phenoxy]-4-(2-methylphenyl)butanoic acid, thought to be the (R)-enantiomer, (1.5 g) in the form of a white solid, m.p. 130-134° C. Chiral HPLC assay showed a 98% enantiomeric excess. [Elemental analysis:- C,71.12; H,5.49;N,6.62%; Calculated:- C,71.64; H,5.47;N, 6.97%].

Aufarbeitung

  1. temperatureis then warmed to 55° C
  2. stirringstirring
  3. waitis continued at 55° C. for 15 hours
  4. temperatureThe reaction mixture is then cooled
  5. concentrationconcentrated in vacuo
  6. additiondiluted with water (100 mL)
  7. extractionis then extracted with ethyl acetate (4×100 mL)
  8. dry with materialThe combined extracts are dried over magnesium sulphate
  9. concentrationconcentrated in vacuo
  10. customto give an oily residue
  11. customThis residue is recrystallized from isopropyl ether

Quellen und Nachweise

ORD-Eintrag
ord-ad7bce4151ce492fb43150d134161164
Quelldatensatz
uspto-grants-2001_04
Patentnummer
US06211234B1

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