4-Methylpyridine → (+/-)-4-[2-(3-Cyclopentyloxymethoxyphenyl)-2-(2-furyl)-2-hydroxyethyl]pyridine

HRID 54596

Reaktionsgleichung

Reaktionsgleichung von HRID 54596
[CH2:1]([Li])CCC.[CH3:6][C:7]1[CH:12]=[CH:11][N:10]=[CH:9][CH:8]=1.[CH:13]1([O:18][C:19]2[CH:20]=[C:21]([C:27]([C:29]3[O:30][CH:31]=[CH:32][CH:33]=3)=[O:28])[CH:22]=[CH:23][C:24]=2OC)CCCC1.[CH2:34]1[CH2:38][O:37][CH2:36][CH2:35]1>>[CH:38]1([O:37][CH2:13][O:18][C:19]2[CH:20]=[C:21]([C:27]([C:29]3[O:30][CH:31]=[CH:32][CH:33]=3)([OH:28])[CH2:6][C:7]3[CH:12]=[CH:11][N:10]=[CH:9][CH:8]=3)[CH:22]=[CH:23][CH:24]=2)[CH2:34][CH2:35][CH2:36][CH2:1]1

Komponenten

5

Edukt 4

HCID 79634-MethylpyridineHCID 8028Tetrahydrofuran2×HCID 19959406(3-Cyclopentyloxy-4-methoxyphenyl)-(2-furyl)ketoneHCID 178418339Butyllithium

Produkt 1

HCID 19959402(+/-)-4-[2-(3-Cyclopentyloxymethoxyphenyl)-2-(2-furyl)-2-hydroxyethyl]pyridineAusbeute 49 %

Reaktionsbedingungen

Temperatur
-70 °C

Versuchsvorschrift

The alcohol (3.2 g) was stirred with manganese (IV) oxide (10 g) in CH2Cl2 (100 ml) at RT for 3 h. The mixture was filtered through Celite® and the filtrate concentrated in vacuo. The residual dark oil was subjected to chromatography (SiO2) to give (3-cyclopentyloxy-4-methoxyphenyl)-(2-furyl)ketone (1.9 g); vmax (neat) 1620cm-1. n-Butyllithium (1.6M solution in hexanes; 4.2 ml, 6.64 mmol) was added to a solution of a 4-methylpyridine (0.62 g, 0.65 ml, 6.64 mmol) in THF (25 ml) at -70° C. After 0.5 h, a solution of the crude ketone (1.9 g, ca 6.6 mmol) in THF (5 ml) was added, stirred for 1 h at -70° C., then at RT fix 0.25 h. The reaction mixture was quenched with water (50 ml) and extracted with EtOAc (3×50 ml). The extract was dried (MgSO4), concentrated in vacuo, and the residual red oil subjected to chromatography (SiO2 ; EtOAc/hexane, 3:2) to afford the title compound (1.23 g, 49%) as a pale yellow oil; δH (CDCl3) 1.5-1.9 (8H, br m, (CH2)4), 2.84 (1H, br s, OH), 3.30 (1H, d, J 13.2 Hz, CHAHB pyridine), 3,59 (1H, d, J 13.2 Hz, CHAHB pyridine), 3.82 (3H, s, OMe), 4.65 (1H, br m OCH), 6.24 (1H-[, dd, J 3.3, 0.7Hz, furan H3), 6.35 (1H, dd, J 3.3, 1.8Hz, furan H4), 6.75-6.85 (3H, m, C6H3), 6.85 (2H, dd, J 4.5, 1.6Hz, pyridine H3,H5), 7.43 (1H, dd, J 1.8, 0.7Hz, furan H5), and 8.33 (2H, dd, J 4.5, 1.6Hz, pyridine H2, H6); m/z (ESI) 402 (M+ +23, 20%), 380 (M+ +1, 35), 287 (100), 95 (28), and 94 (97).

Aufarbeitung

  1. waitat RT fix 0.25 h
  2. customThe reaction mixture was quenched with water (50 ml)
  3. extractionextracted with EtOAc (3×50 ml)
  4. dry with materialThe extract was dried (MgSO4)
  5. concentrationconcentrated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-4984a93a02a645f38f59e4af7ba2b91d
Quelldatensatz
uspto-grants-1997_04
Patentnummer
US05622977

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