Dichloromethane → methyl (S)-2-[3-(2-benzyloxy-1-methylethyl)-2-triethylsilyl-1H-pyrrolo[2,3-b]pyridin-5-yl]-2-methylpropanoate

HRID 609867ノート

反応式

HRID 609867 の反応式
[NH2:1][C:2]1[N:7]=[CH:6][C:5]([C:8]([CH3:14])([CH3:13])[C:9]([O:11][CH3:12])=[O:10])=[CH:4][C:3]=1I.[CH2:16]([O:23][CH2:24][C@@H:25]([CH3:35])[C:26]#[C:27][Si:28]([CH2:33][CH3:34])([CH2:31][CH3:32])[CH2:29][CH3:30])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.C(Cl)Cl.C([O-])([O-])=O.[Na+].[Na+]>C(OCC)(=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].CN(C)C=O>[CH2:16]([O:23][CH2:24][C@H:25]([C:26]1[C:3]2[C:2](=[N:7][CH:6]=[C:5]([C:8]([CH3:14])([CH3:13])[C:9]([O:11][CH3:12])=[O:10])[CH:4]=2)[NH:1][C:27]=1[Si:28]([CH2:33][CH3:34])([CH2:29][CH3:30])[CH2:31][CH3:32])[CH3:35])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1

参加物

8

反応物 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 11323707(S)-(4-benzyloxy-3-methylbut-1-ynyl)triethylsilaneHCID 15887215Methyl 2-(6-amino-5-iodopyridin-3-yl)-2-methylpropanoate

生成物 1

HCID 15887216methyl (S)-2-[3-(2-benzyloxy-1-methylethyl)-2-triethylsilyl-1H-pyrrolo[2,3-b]pyridin-5-yl]-2-methylpropanoate収率 95%

試薬・触媒・溶媒 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
90 °C

実験手順

A vigorously stirred suspension of methyl 2-(6-amino-5-iodopyridin-3-yl)-2-methylpropanoate (4.61 g, 14.4 mmol), (S)-(4-benzyloxy-3-methylbut-1-ynyl)triethylsilane (4.98 g, 17.3 mmol), Pd(dppf)Cl2.CH2Cl2 (0.59 g, 0.72 mmol) LiCl (0.61 g, 14.4 mmol), Na2CO3 (3.82 g, 36.0 mmol) and N,N-dimethylformamide (60 mL) was degassed via three vacuum/nitrogen ingress cycles and the resulting mixture was heated at approximately 90° C. overnight. After cooling to ambient temperature, the reaction mixture was diluted with ethyl acetate and filtered through celite® washing copiously with ethyl acetate. The filtrate was poured into water and extracted with ethyl acetate (×3). The combined organic extract was washed with brine, dried (MgSO4) and concentrated in vacuo. The residue was purified by flash chromatography on silica gel (gradient elution; 20-25% ethyl acetate/hexanes as eluent) to give the title compound as a viscous pale yellow oil (6.11 g, 95%).

後処理

  1. temperatureAfter cooling to ambient temperature
  2. filtrationfiltered through celite®
  3. washwashing copiously with ethyl acetate
  4. additionThe filtrate was poured into water
  5. extractionextracted with ethyl acetate (×3)
  6. extractionThe combined organic extract
  7. washwas washed with brine
  8. dry with materialdried (MgSO4)
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified by flash chromatography on silica gel (gradient elution; 20-25% ethyl acetate/hexanes as eluent)

出典と根拠

ORDレコード
ord-f572f3aa491143b19d41e0dd584deeac
出典データセット
uspto-grants-1999_12
特許番号
US05998432

反応ノート

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