N-methyl-2-pyrrolidone → 2-Ethyl-6-methylisonicotinic acid tert-butyl ester

HRID 1908713

反応式

HRID 1908713 の反応式
[C:1]([O:5][C:6](=[O:15])[C:7]1[CH:12]=[C:11]([CH3:13])[N:10]=[C:9](Cl)[CH:8]=1)([CH3:4])([CH3:3])[CH3:2].CN1C(=O)C[CH2:19][CH2:18]1.C([Mg]Br)C>C1COCC1>[C:1]([O:5][C:6](=[O:15])[C:7]1[CH:12]=[C:11]([CH3:13])[N:10]=[C:9]([CH2:18][CH3:19])[CH:8]=1)([CH3:4])([CH3:3])[CH3:2]

参加物

5

反応物 3

HCID 13387N-methyl-2-pyrrolidoneHCID 860403662-Chloro-6-methyl-isonicotinic acid tert-butyl esterHCID 178418443HCID 178418443、化合物

生成物 1

HCID 670269672-Ethyl-6-methylisonicotinic acid tert-butyl ester

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

実験手順

To a red solution of 2-chloro-6-methyl-isonicotinic acid tert.-butyl ester (2.95 g, 13.0 mmol), Fe(acac)3 (512 mg, 1.45 mmol) and NMP (1.58 g, 16.0 mmol) in THF (400 mL), a solution of ethylmagnesium bromide (1.81 g, 13.6 mmol) in THF is slowly added at −77° C. The brown solution turns green-grey. The suspension is warmed to rt, stirred for 30 min before the yellow solution is again cooled to −70° C. and another portion of the Grignard reagent (1.38 g, 10.4 mmol) is added. The reaction mixture is warmed to rt, stirred for 16 h and then carefully quenched with 1 N aq. HCl (100 mL) and diluted with diethyl ether. The org. layer is separated and the aq. phase is extracted with diethyl ether. The combined org. extracts are dried over MgSO4, filtered and evaporated. The crude product is purified by MPLC on silica gel to give 2-ethyl-6-methyl-isonicotinic acid tert.-butyl ester as a yellow oil which is dissolved in 4 N HCl in dioxane (50 mL). The solution is stirred at 50° C. for 16 h before the solvent is evaporated to give 2-ethyl-6-methylisonicotinic acid hydrochloride as a beige powder; LC-MS: tR=0.28 min; [M+1]+=166.25; 1H NMR (CDCl3): δ 8.19 (s, 2H), 3.12 (q; J=7.6 Hz, 2H), 2.84 (s, 3H), 1.43 (t, J=7.6 Hz, 3H).

後処理

  1. temperatureis again cooled to −70° C.
  2. temperatureThe reaction mixture is warmed to rt
  3. stirringstirred for 16 h
  4. customcarefully quenched with 1 N aq. HCl (100 mL)
  5. additiondiluted with diethyl ether
  6. customlayer is separated
  7. extractionthe aq. phase is extracted with diethyl ether
  8. dry with materialextracts are dried over MgSO4
  9. filtrationfiltered
  10. customevaporated
  11. customThe crude product is purified by MPLC on silica gel

出典と根拠

ORDレコード
ord-d49b1e277b9a4cb18973f72760efeb29
出典データセット
uspto-grants-2013_12
特許番号
US08598208B2

関連ノート

読み込み中…