Toluene → Ethyl 2-methoxy-6-methylisonicotinate

HRID 1908831ノート

反応式

HRID 1908831 の反応式
[CH2:1]([O:3][C:4](=[O:14])[C:5]1[CH:10]=[C:9]([O:11][CH3:12])[N:8]=[C:7](Cl)[CH:6]=1)[CH3:2].[C:15]1(C)C=CC=CC=1>O1CCOCC1.[CH3-].[CH3-].[Zn+2]>[CH2:1]([O:3][C:4](=[O:14])[C:5]1[CH:6]=[C:7]([CH3:15])[N:8]=[C:9]([O:11][CH3:12])[CH:10]=1)[CH3:2]

参加物

5

反応物 2

HCID 1140TolueneHCID 13611989Ethyl 2-chloro-6-methoxyisonicotinate

生成物 1

HCID 45076200Ethyl 2-methoxy-6-methylisonicotinate

試薬・触媒・溶媒 2

HCID 11010Dimethylzinc触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
75 °C

実験手順

Under argon, dimethyl zink (14.26 g, 149 mmol, 124 mL of a 1.2 M solution in toluene) is added dropwise to a solution of 2-chloro-6-methoxy-isonicotinic acid ethyl ester (5.37 g, 24.9 mmol) and Pd(dppf) (203 mg, 0.249 mmol) in dioxane (120 mL). The mixture is heated to 75° C. and stirred for 18 h before it is cooled again to rt. The reaction is quenched by carefully adding water. The mixture is diluted further with water, filtered over celite and the filtrate is extracted with EA (2×250 mL). The combined org. extracts are dried over MgSO4, filtered and concentrated. The crude product is purified by CC on silica gel eluting with heptane:EA 4:1 to give 2-methoxy-6-methyl-isonicotinic acid ethyl ester (4.10 g) as a colourless oil; LC-MS: tR=0.92 min, [M+1]+=195.93. 1H NMR (CDCl3): δ 1.41 (t, J=7.3 Hz, 3H), 2.52 (s, 3H), 3.97 (s, 3H), 4.39 (q, J=7.3 Hz, 2H), 7.12 (s, 1H), 7.28 (s, 1H).

後処理

  1. temperatureis cooled again to rt
  2. customThe reaction is quenched by carefully adding water
  3. additionThe mixture is diluted further with water
  4. filtrationfiltered over celite
  5. extractionthe filtrate is extracted with EA (2×250 mL)
  6. dry with materialextracts are dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude product is purified by CC on silica gel eluting with heptane:EA 4:1

出典と根拠

ORDレコード
ord-8ae5c2665ca54e788feacb3f3f061932
出典データセット
uspto-grants-2013_12
特許番号
US08598208B2

反応ノート

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