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

HRID 1489682

反応式

HRID 1489682 の反応式
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]

参加物

7

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6344Dichloromethane溶媒3 回

反応条件

温度
-70 °C

実験手順

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 dichloromethane (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 dichloromethane (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=8 Hz),7.57(d, 1 H,J=2 Hz),6.95(d, 1H,J=8 Hz),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%].

後処理

  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

出典と根拠

ORDレコード
ord-6712f47f0ee043f78338d3aed1728c65
出典データセット
uspto-grants-1997_10
特許番号
US05679696

関連ノート

読み込み中…