Dimethyl Sulfoxide → 3-Cyclopentyloxy-4-methoxyphenyl 3,5-dichloropyrid-4-ylmethyl ketone

HRID 356899

Reaktionsgleichung

Reaktionsgleichung von HRID 356899
C(Cl)(=O)C(Cl)=O.CS(C)=O.[CH:11]1([O:16][C:17]2[CH:18]=[C:19]([CH:25]([OH:35])[CH2:26][C:27]3[C:32]([Cl:33])=[CH:31][N:30]=[CH:29][C:28]=3[Cl:34])[CH:20]=[CH:21][C:22]=2[O:23][CH3:24])[CH2:15][CH2:14][CH2:13][CH2:12]1.C(N(CC)CC)C>ClCCl.O>[Cl:33][C:32]1[CH:31]=[N:30][CH:29]=[C:28]([Cl:34])[C:27]=1[CH2:26][C:25]([C:19]1[CH:20]=[CH:21][C:22]([O:23][CH3:24])=[C:17]([O:16][CH:11]2[CH2:15][CH2:14][CH2:13][CH2:12]2)[CH:18]=1)=[O:35]

Komponenten

7

Edukt 4

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 216976801-(3-Cyclopentyloxy-4-methoxyphenyl)-2-(3,5-dichloropyrid-4-yl)ethanol

Produkt 1

HCID 214695783-Cyclopentyloxy-4-methoxyphenyl 3,5-dichloropyrid-4-ylmethyl ketone

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6344DichloromethaneLösungsmittel3×

Reaktionsbedingungen

Temperatur
-70 °C

Versuchsvorschrift

A solution of oxalyl chloride (5.3 mL) in dry dichloromethane (125 mL) at -60° C. is treated portionwise with dimethyl sulfoxide (9.1 mL) in dichloro- methane (20 mL), keeping the temperature below -50° C. The solution is then stirred at -70° C. for 20 minutes and is then treated with a suspension of 1-(3-cyclopentyloxy-4-methoxyphenyl)-2-(3,5-dichloropyrid-4-yl)ethanol (20.5 g; that is prepared as described in Reference Example 63) in dry dichloro -methane (300 mL) during 20 minutes, keeping the temperature below -50° C. After stirring for 30 minutes, the solution is treated with triethylamine (35 mL) and allowed to rise to room temperature. It is then treated with water (250 mL) and extracted with ethyl acetate (2×100 mL). The combined organic extracts are washed with dilute sulfuric acid (100 mL; 1%), aqueous potassium carbonate solution (100 ml; 5%) and brine (100 mL), dried and concentrated and the resulting residue is recrystallized from a mixture of ethyl acetate and heptane, to give 3-cyclopentyloxy-4-methoxyphenyl 3,5-dichloropyrid-4-ylmethyl ketone (19.6 g), m.p. 119°-120° C. [NMR(CDCl3): 8.52(s,2H),7.69 (dd, 1H,J=8Hz),7.57(d,1H,J=2Hz),6.95(d,1H,J=8Hz),4.86 (m,1H),4.64(s,2H), 3.95(s,3H),2.05-1.58(m,8H). Elemental analysis: C,59.8,H,4.95,N,3.63%; calculated: C,60.0,H,5.0,N,3.7%].

Aufarbeitung

  1. customthe temperature below -50° C
  2. customthat is prepared
  3. customduring 20 minutes
  4. customthe temperature below -50° C
  5. stirringAfter stirring for 30 minutes
  6. customto rise to room temperature
  7. extractionextracted with ethyl acetate (2×100 mL)
  8. washThe combined organic extracts are washed with dilute sulfuric acid (100 mL; 1%), aqueous potassium carbonate solution (100 ml; 5%) and brine (100 mL)
  9. customdried
  10. concentrationconcentrated
  11. customthe resulting residue is recrystallized from a mixture of ethyl acetate and heptane

Quellen und Nachweise

ORD-Eintrag
ord-e2d7f8de21454db19b1e7088d599f473
Quelldatensatz
uspto-grants-1998_11
Patentnummer
US05840724

Verknüpfte Notizen

Wird geladen…