Reaktion #11419

Reaktionsgleichung

sodium hydride

ethyl 2-bromoacetate

5-(4-hydroxy-phenyl)-6-methyl-2-oxo-1,2-dihydro-pyridine-3-carbonitrile

5-(4-Hydroxy-phenyl)-6-methyl-2-oxo-1,2-dihydropyridine-3-carbonitrile

→

[4-(5-Cyano-2-methyl-6-oxo-1,6-dihydro-pyridin-3-yl)phenoxy]-acetic acid ethyl ester

Ausbeute 29.0%

Lösungsmittel

N,N-dimethylformamide

N,N-dimethylformamide

N,N-dimethylformamide

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGthe mixture was stirred for 30 min at 0° C., for 30 min at ambient temperature
2. 2
   workup.WAITfor 45 min at 80° C
3. 3
   Temperaturto cool to room temperature
4. 4
   Einengenconcentrated in vacuo
5. 5
   workup.DISSOLUTIONre-dissolved in ethyl acetate (300 mL)
6. 6
   ExtraktionThe solution was extracted with water (3×150 mL)
7. 7
   Extraktionextracted with ethyl acetate (3×150 mL)
8. 8
   TrocknenThe combined organic layers were dried (MgSO4)
9. 9
   Sonstigeevaporated to dryness
10. 10
    SonstigeThe residue was purified by column chromatography on silica gel (50 g)

Vorschrift

To a stirred suspension of sodium hydride (60% dispersion in mineral oil, 1.16 g, 29.0 mmol) in N,N-dimethylformamide (50 mL), was added at 0° C. a solution of 5-(4-hydroxy-phenyl)-6-methyl-2-oxo-1,2-dihydro-pyridine-3-carbonitrile (6, 3.25 g, 14.4 mmol) in N,N-dimethylformamide (50 mL). The mixture was stirred at ambient temperature for 30 min. A solution of ethyl 2-bromoacetate (2.0 mL, 18.0 mmol) in N,N-dimethylformamide (10 mL) was added at 0° C., the mixture was stirred for 30 min at 0° C., for 30 min at ambient temperature and then for 45 min at 80° C. The mixture was allowed to cool to room temperature, concentrated in vacuo and re-dissolved in ethyl acetate (300 mL). The solution was extracted with water (3×150 mL). The combined aqueous layers were acidified to pH 2 with aqueous hydrochloric acid (1 N) and extracted with ethyl acetate (3×150 mL). The combined organic layers were dried (MgSO4) and evaporated to dryness. The residue was purified by column chromatography on silica gel (50 g) using 2% methanol in dichloromethane as eluent to give [4-(5-Cyano-2-methyl-6-oxo-1,6-dihydro-pyridin-3-yl)phenoxy]-acetic acid ethyl ester (7) as light yellow powder (1.3 g, 29% yield, 80–90% pure by LC-MS and 1H NMR), 1H NMR (400 MHz; CDCl3): δ 7.70 (d, 1H); 7.19 (m, 2H); 6.72 (m, 2H); 4.90 (s, 2H); 4.12 (q, 2H); 1.71 (s, 3H); 1.30 (t, 3H).

Quelle