Lithium Chloride → Methyl 4-(2-ethoxyvinyl)-1-(4-fluorobenzyl)-1H-pyrrolo[2,3-c]pyridine-5-carboxylate

HRID 640698ノート

反応式

HRID 640698 の反応式
[F:1][C:2]1[CH:29]=[CH:28][C:5]([CH2:6][N:7]2[C:11]3=[CH:12][N:13]=[C:14]([C:24]([O:26][CH3:27])=[O:25])[C:15](OS(C(F)(F)F)(=O)=O)=[C:10]3[CH:9]=[CH:8]2)=[CH:4][CH:3]=1.[Cl-].[Li+].[CH2:32]([O:34][CH:35]=[CH:36][Sn](CCCC)(CCCC)CCCC)[CH3:33]>CN(C=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH2:35]([O:34][CH:32]=[CH:33][C:15]1[C:14]([C:24]([O:26][CH3:27])=[O:25])=[N:13][CH:12]=[C:11]2[N:7]([CH2:6][C:5]3[CH:28]=[CH:29][C:2]([F:1])=[CH:3][CH:4]=3)[CH:8]=[CH:9][C:10]=12)[CH3:36]

参加物

6

反応物 3

HCID 433294Lithium ChlorideHCID 2763294(Z)-1-Ethoxy-2-(tributylstannyl)etheneHCID 532374681h-Pyrrolo[2,3-c]pyridine-5-carboxylic acid,1-[(4-fluorophenyl)methyl]-4-[[(trifluoromethyl)sulfonyl]oxy]-,methyl ester

生成物 1

HCID 68665270Methyl 4-(2-ethoxyvinyl)-1-(4-fluorobenzyl)-1H-pyrrolo[2,3-c]pyridine-5-carboxylate収率 89.2%

試薬・触媒・溶媒 2

HCID 178418476HCID 178418476、化合物触媒HCID 6228Dimethylformamide溶媒2 回

反応条件

温度
79 °C

実験手順

To a solution of methyl 1-(4-fluorobenzyl)-4-{[(trifluoromethyl)sulfonyl]oxy}-1H-pyrrolo[2,3-c]pyridine-5-carboxylate (2 g, 4.62 mmol) in DMF (27 mL) was added lithium chloride (0.59 mg, 13.88 mmol). Dry nitrogen was bubbled through the mixture for for 10 min, and then dichlorobis(triphenylphosphine)palladium(II) (0.16 g, 0.23 mmol) was added. The mixture was heated to 79° C., and a solution of ethoxyvinyl tributyltin (mixture of isomers: 1,2-E:1,2-Z:1,1=1:0: 0.97:0.18) [prepared according to A. Leusik, H. A. Budding, J. W. Marsman, J. Organomet. Chem., 1967, 9, 285-294] (1.82 g, 5.08 mmol) in DMF (23 mL). The resulting mixture was stirred for 9 h at 70° C. under nitrogen atmosphere. It was quenched with saturated sodium chloride and filtered to remove solid precipitate then concentrated. Purification by flash chromatography (Biotage) over silica gel (1:1 to 1:3, hexane/ethyl acetate) afforded the title product as brown glue (1.46 g, 89.2% yield). LCMS (APCl, M+H+): 355.2.

後処理

  1. customDry nitrogen was bubbled through the mixture for for 10 min
  2. customIt was quenched with saturated sodium chloride
  3. filtrationfiltered
  4. customto remove solid precipitate
  5. concentrationthen concentrated
  6. customPurification by flash chromatography (Biotage) over silica gel (1:1 to 1:3, hexane/ethyl acetate)

出典と根拠

ORDレコード
ord-3f6e3e12e082489a96a0d48f20c487f0
出典データセット
uspto-grants-2010_04
特許番号
US07692014B2

反応ノート

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