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

HRID 864852

반응식

HRID 864852 반응식
[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]

참가 물질

5

반응물 3

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

생성물 1

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

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

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) δ13.45(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%.

후처리

  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)

출처 및 근거

ORD 기록
ord-e17ac3892ab34141b23685a0ecbc2d8d
출처 데이터셋
uspto-grants-1996_10
특허 번호
US05563141

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