Sodium hydride → Ethyl 3-methyl-4-[4-[4-(4-pyridyl)piperazin-1-yl]phenoxy]butyrate

HRID 266763

Reaktionsgleichung

Reaktionsgleichung von HRID 266763
[N:1]1[CH:6]=[CH:5][C:4]([N:7]2[CH2:12][CH2:11][N:10]([C:13]3[CH:18]=[CH:17][C:16]([OH:19])=[CH:15][CH:14]=3)[CH2:9][CH2:8]2)=[CH:3][CH:2]=1.[H-].[Na+].[CH2:22]([O:24][C:25](=[O:31])[CH2:26][CH:27]([CH3:30])[CH2:28]Br)[CH3:23]>CN(C=O)C>[CH3:28][CH:27]([CH2:30][O:19][C:16]1[CH:17]=[CH:18][C:13]([N:10]2[CH2:9][CH2:8][N:7]([C:4]3[CH:5]=[CH:6][N:1]=[CH:2][CH:3]=3)[CH2:12][CH2:11]2)=[CH:14][CH:15]=1)[CH2:26][C:25]([O:24][CH2:22][CH3:23])=[O:31]

Komponenten

5

Edukt 3

HCID 24758Sodium hydrideHCID 149869034-(4-(4-Pyridyl)piperazin-1-yl)phenolHCID 18918405Ethyl-4-bromo-3-methylbutyrate

Produkt 1

HCID 18918316Ethyl 3-methyl-4-[4-[4-(4-pyridyl)piperazin-1-yl]phenoxy]butyrate

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

To a stirred suspension of 4-[4-(4-pyridyl)piperazin-1-yl]phenol (1.02 g) in dry DMF (10 ml) was added sodium hydride (60% dispersion in mineral oil, 0.16 g) and the mixture stirred for 1 hour at room temperature. To the resulting solution was added ethyl-4-bromo-3-methylbutyrate and the mixture stirred for 16 hours. Solvent was evaporated and the residue partitioned between water and dichloromethane. Insoluble material was removed by centrifugation. The organic layer was filtered through phase separating paper (Whatman IPS) and the residue was purified by flash chromatography on silica gel by elution with methanol/dichloromethane/concentrated ammonia (50/950/5) to give ethyl 3-methyl-4-[4-[4-(4-pyridyl)piperazin-1-yl]phenoxy]butyrate (0.27 g) which was hydrolysed in methanol (3 ml) and aqueous sodium hydroxide (1N, 2 ml) for 2 hours at room temperature. The solution was evaporated and the residue purified by reverse phase h.p.l.c (water/acetonitrile/0.1% TFA gradient) to give a glass which crystallised on trituration with ether to give the title compound (0.08 g): m.p. 169°-171° C.; NMR(d6DMSO) δ 13.45(1H,broad), 12.07(1H,broad) 8.27(2H,d), 7.28(2H,d), 6.9(4H,m), 3.80(6H,m), 3.16(4H,t), 2.45(1H,m), 2.37(1H,m), 2.12(1H,m), 1.0(3H,d); m/e 356(M+H)+ ; calculated for C22H25N3O4F3. 0.5 H2O: C, 55.2; H, 5.6; N, 8.9. Found: C, 55.3; H, 5.6; N, 8.7%.

Aufarbeitung

  1. stirringthe mixture stirred for 16 hours
  2. customSolvent was evaporated
  3. customthe residue partitioned between water and dichloromethane
  4. customInsoluble material was removed by centrifugation
  5. filtrationThe organic layer was filtered through phase
  6. customseparating paper (Whatman IPS)
  7. customthe residue was purified by flash chromatography on silica gel by elution with methanol/dichloromethane/concentrated ammonia (50/950/5)

Quellen und Nachweise

ORD-Eintrag
ord-f275502c8f8147c0912efaa56673d75c
Quelldatensatz
uspto-grants-1997_07
Patentnummer
US05652242

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