N-methyl-2-pyrrolidone → HCID 67026912、化合物

HRID 2065871ノート

反応式

HRID 2065871 の反応式
[C:1]([O:5][C:6](=[O:15])[C:7]1[CH:12]=[C:11](Cl)[C:10]([CH3:14])=[N:9][CH:8]=1)([CH3:4])([CH3:3])[CH3:2].CN1C(=O)CCC1.[CH2:23]([Mg]Br)[CH:24]([CH3:26])[CH3:25].C[Mg]Br>C1COCC1>[C:1]([O:5][C:6](=[O:15])[C:7]1[CH:12]=[C:11]([CH2:23][CH:24]([CH3:26])[CH3:25])[C:10]([CH3:14])=[N:9][CH:8]=1)([CH3:4])([CH3:3])[CH3:2]

参加物

6

反応物 4

HCID 13387N-methyl-2-pyrrolidoneHCID 670268835-Chloro-6-methylnicotinic acid tert-butyl esterHCID 178418573HCID 178418573、化合物HCID 178418816HCID 178418816、化合物

生成物 1

HCID 67026912HCID 67026912、化合物

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒3 回

反応条件

温度
-78 °C

実験手順

5-Chloro-6-methyl-nicotinic acid tert.-butyl ester (3.09 g, 13.5 mmol), Fe(acac)3 (719 mg, 2.04 mmol) and NMP (1.95 mL, 20 mmol) are dissolved in THF (3M, 500 mL) and cooled at −78° C. A solution of isobutylmagnesium bromide in THF (2M, 13.6 mmol) is slowly added at −75° C. The brown solution turns turbid and yellow. Stirring is continued for 1 h at −75° C. before it is slowly warmed to rt. The reaction is incomplete, further Fe(acac)3 (719 mg, 2.04 mmol) is added and the mixture is cooled again at −70° C. Further methylmagnesium bromide in THF (2M, 13.6 mmol) is slowly added at −70° C. The dark green mixture is slowly warmed to rt and stirred for 15 h. The mixture is carefully quenched with 0.7N aq. HCl (150 mL). The mixture is extracted with EA (6×60 mL). The combined org. extracts are dried over Na2SO4, filtered and evaporated. The residue is purified by reversed phase MPLC to give 6-methyl-5-isobutyl-nicotinic acid tert.-butyl ester as black oil (0.50 g); LC-MS: tR=0.84 min, [M+1]+=250.14.

後処理

  1. temperatureis slowly warmed to rt
  2. temperaturethe mixture is cooled again at −70° C
  3. temperatureThe dark green mixture is slowly warmed to rt
  4. stirringstirred for 15 h
  5. customThe mixture is carefully quenched with 0.7N aq. HCl (150 mL)
  6. extractionThe mixture is extracted with EA (6×60 mL)
  7. dry with materialextracts are dried over Na2SO4
  8. filtrationfiltered
  9. customevaporated
  10. customThe residue is purified by reversed phase MPLC

出典と根拠

ORDレコード
ord-338b071cab72447b948a948448b9be2c
出典データセット
uspto-grants-2012_10
特許番号
US08288554B2

反応ノート

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