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 502919노트

반응식

HRID 502919 반응식
[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

참가 물질

7

반응물 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

생성물 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

시약·촉매·용매 1

HCID 6342Acetonitrile용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-3526f4b4621e487fa6875796ccc6831b
출처 데이터셋
uspto-grants-2010_08
특허 번호
US07776888B2

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