Acetone Cyanohydrin → 3-[2-(2-Methoxy-ethoxymethyl)-6-trifluoromethyl-pyridine-3-carbonyl]-1,5-dimethyl-8-oxa-bicyclo[3.2.1]oct-6-ene-2,4-dione

HRID 502919ノート

反応式

HRID 502919 の反応式
[CH3:1][C:2]12[O:9][C:6]([CH3:10])([CH:7]=[CH:8]1)[C:5](=[O:11])[CH2:4][C:3]2=[O:12].[CH3:13][O:14][CH2:15][CH2:16][O:17][CH2:18][C:19]1[N:27]=[C:26]([C:28]([F:31])([F:30])[F:29])[CH:25]=[CH:24][C:20]=1[C:21](O)=[O:22].C1(N=C=NC2CCCCC2)CCCCC1.C(N(CC)CC)C.CC(C)(O)C#N>C(#N)C>[CH3:13][O:14][CH2:15][CH2:16][O:17][CH2:18][C:19]1[C:20]([C:21]([CH:4]2[C:3](=[O:12])[C:2]3([CH3:1])[O:9][C:6]([CH3:10])([CH:7]=[CH:8]3)[C:5]2=[O:11])=[O:22])=[CH:24][CH:25]=[C:26]([C:28]([F:31])([F:29])[F:30])[N:27]=1

参加物

7

反応物 5

HCID 6406Acetone CyanohydrinHCID 8471TriethylamineHCID 10868DicyclohexylcarbodiimideHCID 113349532-(2-Methoxy-ethoxymethyl)-6-trifluoromethyl-nicotinic acidHCID 586095231,5-Dimethyl-8-oxa-bicyclo[3.2.1]oct-6-ene-2,4-dione

生成物 1

HCID 586095343-[2-(2-Methoxy-ethoxymethyl)-6-trifluoromethyl-pyridine-3-carbonyl]-1,5-dimethyl-8-oxa-bicyclo[3.2.1]oct-6-ene-2,4-dione

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒

実験手順

146 mg (0.879 mmol) of 1,5-dimethyl-8-oxa-bicyclo[3.2.1]oct-6-ene-2,4-dione and 245 mg (0.879 mmol) of 2-(2-methoxy-ethoxymethyl)-6-trifluoromethyl-nicotinic acid (preparation as described in WO 01/94339) are dissolved in 29 ml of acetonitrile and treated at ambient temperature with 199 mg (0.966 mmol) of dicyclohexylcarbodiimide. The reaction mixture is stirred for 2 hours and then 0.184 ml (1.318 mmol) of triethylamine and 0.08 ml (0.879 mmol) of acetone cyanohydrin are added. Stirring is carried out for a further 16 hours at ambient temperature, followed by concentration under reduced pressure. The residue that remains behind is chromatographed over silica gel (eluant: toluene/ethanol/dioxane/triethylamine/water 20:8:4:4:1). The product-containing fraction is concentrated. The oily residue is again dissolved in fresh ethyl acetate and washed with 10 ml of dilute hydrochloric acid (pH 1), and then with water (2×) and sodium chloride solution (2×). After the solution has been dried over sodium sulfate and concentrated by evaporation under reduced pressure, 128 mg (34%) of 3-[2-(2-methoxy-ethoxymethyl)-6-trifluoromethyl-pyridine-3-carbonyl]-1,5-dimethyl-8-oxa-bicyclo[3.2.1]oct-6-ene-2,4-dione are obtained in the form of a yellow oil.

後処理

  1. stirringStirring
  2. waitis carried out for a further 16 hours at ambient temperature
  3. concentrationfollowed by concentration under reduced pressure
  4. customThe residue that remains behind is chromatographed over silica gel (eluant: toluene/ethanol/dioxane/triethylamine/water 20:8:4:4:1)
  5. concentrationThe product-containing fraction is concentrated
  6. dissolutionThe oily residue is again dissolved in fresh ethyl acetate
  7. washwashed with 10 ml of dilute hydrochloric acid (pH 1)
  8. dry with materialAfter the solution has been dried over sodium sulfate
  9. concentrationconcentrated by evaporation under reduced pressure, 128 mg (34%) of 3-[2-(2-methoxy-ethoxymethyl)-6-trifluoromethyl-pyridine-3-carbonyl]-1,5-dimethyl-8-oxa-bicyclo[3.2.1]oct-6-ene-2,4-dione
  10. customare obtained in the form of a yellow oil

出典と根拠

ORDレコード
ord-3526f4b4621e487fa6875796ccc6831b
出典データセット
uspto-grants-2010_08
特許番号
US07776888B2

反応ノート

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