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

HRID 922577

반응식

HRID 922577 반응식
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

참가 물질

6

반응물 3

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

생성물 1

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

시약·촉매·용매 2

HCID 10129912Zinc(II) fluoride촉매HCID 6228Dimethylformamide용매

반응 조건

온도
85 °C

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-e8e07004844e4b09aedabc9266e5beff
출처 데이터셋
uspto-grants-2016_03
특허 번호
US09278953B2

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