2',5'-Dimethoxyacetophenone → 2-(3,4-Difluoro-5-methoxyphenyl)-1-(2,5-dimethoxyphenyl)ethanone

HRID 2368922ノート

反応式

HRID 2368922 の反応式
C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.CC([O-])(C)C.[Na+].Br[C:54]1[CH:55]=[C:56]([O:62][CH3:63])[C:57]([F:61])=[C:58]([F:60])[CH:59]=1.[CH3:64][O:65][C:66]1[CH:71]=[CH:70][C:69]([O:72][CH3:73])=[CH:68][C:67]=1[C:74](=[O:76])[CH3:75]>C1COCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O>[F:60][C:58]1[CH:59]=[C:54]([CH2:75][C:74]([C:67]2[CH:68]=[C:69]([O:72][CH3:73])[CH:70]=[CH:71][C:66]=2[O:65][CH3:64])=[O:76])[CH:55]=[C:56]([O:62][CH3:63])[C:57]=1[F:61]

参加物

8

反応物 4

HCID 709912',5'-DimethoxyacetophenoneHCID 634876Binap, (A+-)-HCID 27732885-Bromo-1,2-difluoro-3-methoxybenzeneHCID 23676156Sodium t-butoxide

生成物 1

HCID 866828992-(3,4-Difluoro-5-methoxyphenyl)-1-(2,5-dimethoxyphenyl)ethanone収率 24.8%

試薬・触媒・溶媒 3

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
70 °C

実験手順

A 100-mL round-bottom flask charged with Pd2dba3 (69 mg, 0.075 mmol), BINAP (112 mg, 0.18 mmol), and NaOt−Bu (650 mg, 6.5 mmol) was degassed and filled with N2. THF (20 mL) was added, followed by a solution 5-bromo-1,2-difluoro-3-methoxybenzene (1.1 g, 5 mmol) and 1-(2,5-dimethoxyphenyl)ethanone (1.08 g, 6 mmol) in THF (10 mL). The resulting mixture was heated at 70° C. for 16 h. Water (30 mL) was added, and the mixture was extracted with ether (3×50 mL). The combined organics were dried over anhydrous Na2SO4, filtered, and concentrated to give the crude product, which was purified by column chromatography on silica gel (eluting with petroleum ether/ethyl acetate=80/1˜40/1) to give 2-(3,4-difluoro-5-methoxyphenyl)-1-(2,5-dimethoxyphenyl)ethanone (0.4 g) as a light yellow solid. 1H NMR (CDCl3): δ 7.24 (d, 1H), 7.04 (dd, 1H), 6.92 (d, 1H), 6.68-6.61 (m, 2H), 4.23 (s, 2H), 3.90 (s, 3H), 3.87 (s, 3H), 3.78 (s, 3H); LCMS: 323 (M+H)+.

後処理

  1. customwas degassed
  2. additionfilled with N2
  3. additionTHF (20 mL) was added
  4. extractionthe mixture was extracted with ether (3×50 mL)
  5. dry with materialThe combined organics were dried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give the crude product, which
  9. customwas purified by column chromatography on silica gel (eluting with petroleum ether/ethyl acetate=80/1˜40/1)

出典と根拠

ORDレコード
ord-7bd0cafdf63846728732f4335e7acbf6
出典データセット
uspto-grants-2014_04
特許番号
US08703810B2

反応ノート

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