Sodium Chloride → 5-Methoxy-6-methyl-1H-indene-3-carbonitrile

HRID 499008

反応式

HRID 499008 の反応式
[CH3:1][O:2][C:3]1[CH:11]=[C:10]2[C:6]([CH2:7][CH2:8][C:9]2=O)=[CH:5][C:4]=1[CH3:13].[C:14](P(=O)(OCC)OCC)#[N:15].[C-]#N.[Li+].[Cl-].[Na+].B(F)(F)F.CCOCC>C1COCC1.O>[CH3:1][O:2][C:3]1[CH:11]=[C:10]2[C:6](=[CH:5][C:4]=1[CH3:13])[CH2:7][CH:8]=[C:9]2[C:14]#[N:15]

参加物

8

反応物 5

HCID 5234Sodium ChlorideHCID 8000Boron trifluoride etherateHCID 75478Lithium cyanide2 回HCID 76257Diethyl cyanophosphonate2 回HCID 123863856-Methoxy-5-methyl-2,3-dihydro-1H-inden-1-one

生成物 1

HCID 450913555-Methoxy-6-methyl-1H-indene-3-carbonitrile収率 24.8%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
45 °C

実験手順

A solution of 10.7 grams (0.061 mole) of 6-methoxy-5-methylindan-1-one (ii), 29.7 grams (0.182 mole) of diethyl cyanophosphonate, and 6.1 grams (0.182 mole) of lithium cyanide in 250 mL of anhydrous THF was stirred at ambient temperature for five hours. GC analysis of the reaction mixture indicated that the reaction was not complete. The reaction mixture was warmed to 45° C., where it was stirred for about 16 hours. After this time, an aliquot of the reaction mixture was placed water and the mixture was extracted with ethyl acetate. GC analysis of the extract indicated that the reaction was about 10% complete. An additional 0.182 mole each of diethyl cyanophosphonate and lithium cyanide were added to the reaction mixture, and heating at 45° C. was continued for about an additional eight hours. After this time, the reaction mixture was poured into about 300 mL of an aqueous solution saturated with sodium chloride, and then it was extracted with two 300 mL portions of ethyl acetate. The combined extracts were then washed with three portions of an aqueous solution saturated with sodium chloride and dried with sodium sulfate. The mixture was filtered and the filtrate was concentrated under reduced pressure to a residue. The residue was dissolved in toluene and again concentrated under reduced pressure to a residue. The residue was taken up in 500 mL of toluene and 20.7 grams (0.182 mole) of boron trifluoride diethyl etherate was added. Upon completion of addition, the reaction mixture was stirred at ambient temperature for about six hours. The reaction mixture was treated as set forth above, yielding a residue. The residue was purified by column chromatography on silica gel using mixtures of hexane and diethyl ether as an eluant. The appropriate fractions of eluate were combined and concentrated under reduced pressure, yielding 2.8 grams of subject compound. The NMR spectrum was consistent with the proposed structure.

後処理

  1. extractionthe mixture was extracted with ethyl acetate
  2. temperatureheating at 45° C.
  3. customwas continued for about an additional eight hours
  4. extractionit was extracted with two 300 mL portions of ethyl acetate
  5. washThe combined extracts were then washed with three portions of an aqueous solution saturated with sodium chloride
  6. dry with materialdried with sodium sulfate
  7. filtrationThe mixture was filtered
  8. concentrationthe filtrate was concentrated under reduced pressure to a residue
  9. dissolutionThe residue was dissolved in toluene
  10. concentrationagain concentrated under reduced pressure to a residue
  11. additionUpon completion of addition
  12. stirringthe reaction mixture was stirred at ambient temperature for about six hours
  13. additionThe reaction mixture was treated
  14. customyielding a residue
  15. customThe residue was purified by column chromatography on silica gel using mixtures of hexane and diethyl ether as an eluant
  16. concentrationconcentrated under reduced pressure

出典と根拠

ORDレコード
ord-66c11a75cfb84f8b987f16e32223ccef
出典データセット
uspto-grants-2010_08
特許番号
US07767667B2

関連ノート

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