N-methyl-2-pyrrolidone → HCID 67026912, 화합물

HRID 2065871노트

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HRID 2065871 반응식
[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]

참가 물질

6

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HCID 13387N-methyl-2-pyrrolidoneHCID 670268835-Chloro-6-methylnicotinic acid tert-butyl esterHCID 178418573HCID 178418573, 화합물HCID 178418816HCID 178418816, 화합물

생성물 1

HCID 67026912HCID 67026912, 화합물

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매3회

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온도
-78 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-338b071cab72447b948a948448b9be2c
출처 데이터셋
uspto-grants-2012_10
특허 번호
US08288554B2

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