1-Methoxy-1-trimethylsilyloxypropene → Methyl 2-(6-chloro-2-methoxypyridin-3-yl)propanoate

HRID 922577

反応式

HRID 922577 の反応式
Br[C:2]1[C:3]([O:9][CH3:10])=[N:4][C:5]([Cl:8])=[CH:6][CH:7]=1.C(P(C(C)(C)C)C(C)(C)C)(C)(C)C.C1(C)C=CC=CC=1.[CH3:31][O:32]/[C:33](/[O:36][Si](C)(C)C)=[CH:34]\[CH3:35]>CN(C=O)C.[F-].[Zn+2].[F-]>[Cl:8][C:5]1[N:4]=[C:3]([O:9][CH3:10])[C:2]([CH:34]([CH3:35])[C:33]([O:32][CH3:31])=[O:36])=[CH:7][CH:6]=1

参加物

6

反応物 3

HCID 108557751-Methoxy-1-trimethylsilyloxypropeneHCID 532174543-Bromo-6-chloro-2-methoxypyridineHCID 66647975Tri-t-butylphosphine toluene

生成物 1

HCID 117992989Methyl 2-(6-chloro-2-methoxypyridin-3-yl)propanoate収率 64%

試薬・触媒・溶媒 2

HCID 10129912Zinc(II) fluoride触媒HCID 6228Dimethylformamide溶媒

反応条件

温度
85 °C

実験手順

To a dry flask was added 3-bromo-6-chloro-2-methoxypyridine (9.7 g, 43.7 mmol), palladium(0)bis(dibenzylideneacetone) (1.3 g, 2.2 mmol), and zinc fluoride (3.4 g, 32.7 mmol). The mixture was degassed with nitrogen. A solution of tri-tert-butylphoshine/toluene (1.0 M, 4.4 mL, 4.4 mmol) in DMF (146 mL) was then added to the degassed mixture. After stirring, (E)-(1-methoxyprop-1-enyloxy)trimethylsilane (15.2 mL, 65 mmol) was added and the reaction was heated at 85° C. for 18 h. The mixture was partitioned between MTBE and brine. The aqueous layer was extracted with MTBE. The combined organic layers were dried over Na2SO4 and concentrated. Purification by silica gel column chromatography (330 g RediSep Gold column, 30-65% DCM/heptanes) provided methyl 2-(6-chloro-2-methoxypyridin-3-yl)propanoate (6.4 g, 64%); 1H NMR (600 MHz, CDCl3) δ: 1.44 (d, 3H), 3.67 (s, 3H), 3.91 (q, 1H), 3.95 (s, 3H), 6.89 (d, 1H), 7.45 (d, 1H).

後処理

  1. customThe mixture was degassed with nitrogen
  2. customThe mixture was partitioned between MTBE and brine
  3. extractionThe aqueous layer was extracted with MTBE
  4. dry with materialThe combined organic layers were dried over Na2SO4
  5. concentrationconcentrated
  6. customPurification by silica gel column chromatography (330 g RediSep Gold column, 30-65% DCM/heptanes)

出典と根拠

ORDレコード
ord-e8e07004844e4b09aedabc9266e5beff
出典データセット
uspto-grants-2016_03
特許番号
US09278953B2

関連ノート

読み込み中…