Dichloromethane → 4-[3-(2-Fluoro-pyridin-3-yl)-indole-1-sulfonyl]-benzoic acid methyl ester

HRID 1178921ノート

反応式

HRID 1178921 の反応式
[CH3:1][O:2][C:3](=[O:23])[C:4]1[CH:9]=[CH:8][C:7]([S:10]([N:13]2[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[C:15](I)=[CH:14]2)(=[O:12])=[O:11])=[CH:6][CH:5]=1.[F:24][C:25]1[C:30](B(O)O)=[CH:29][CH:28]=[CH:27][N:26]=1.C(=O)([O-])[O-].[Na+].[Na+].ClCCl>C1COCC1>[CH3:1][O:2][C:3](=[O:23])[C:4]1[CH:9]=[CH:8][C:7]([S:10]([N:13]2[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[C:15]([C:30]3[C:25]([F:24])=[N:26][CH:27]=[CH:28][CH:29]=3)=[CH:14]2)(=[O:12])=[O:11])=[CH:6][CH:5]=1

参加物

6

反応物 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 27832702-Fluoropyridine-3-boronic acidHCID 58974999Benzoic acid,4-[(3-iodo-1h-indol-1-yl)sulfonyl]-,methyl ester

生成物 1

HCID 670231694-[3-(2-Fluoro-pyridin-3-yl)-indole-1-sulfonyl]-benzoic acid methyl ester

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

Reflux a mixture of 4-(3-iodo-indole-1-sulfonyl)-benzoic acid methyl ester (1.33 g, 3.01 mmol, 1 equiv), 2-fluoropyridine-3-boronic acid (Frontier Scientific®; 0.47 g, 3.3 mmol, 1.1 equiv), sodium carbonate (2M in H2O; 3.0 mL, 6.0 mmol, 2.0 equiv), and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (62 mg, 0.080 mmol, 0.025 equiv) in THF (15 mL) under N2 for 2 h (reaction mixture turned very dark when heated). Rotary evaporate the reaction mixture. Dissolve the resultant residue in Et2O (15 mL) and wash with H2O (5 mL). Back-extract the aqueous layer is with Et2O (5 mL). Dry the combined organic layers with (anhydr Na2SO4), and rotary evaporate (40° C.) giving the crude 4-[3-(2-fluoro-pyridin-3-yl)-indole-1-sulfonyl]-benzoic acid methyl ester as a brown foam. Dissolve this material in THF (10 mL) and add 5M aq NaOH (2 mL). After 18 h, add H2O (25 mL) and Et2O (25 mL). Separate the aqueous layer and extract the organic layer with H2O (25 mL). Combine the aqueous layers and wash with Et2O (25 mL). Acidify this aqueous layer with 1M aq HCl (8 mL) to pH 5 causing much precipitation. Extract this mixture with CHCl3 (1×50 mL, 2×25 mL). Dry the combined organic layers (anhydr Na2SO4) and rotary evaporate (40° C.) yielding 673 mg (56.3%) of 4-[3-(2-fluoro-pyridin-3-yl)-indole-1-sulfonyl]-benzoic acid as a brown powder. MS (m/e): 396.94 (M+1); 394.99 (M−1).

後処理

  1. temperatureReflux
  2. customreaction mixture
  3. temperatureheated)
  4. customRotary evaporate the reaction mixture
  5. dissolutionDissolve the resultant residue in Et2O (15 mL)
  6. washwash with H2O (5 mL)
  7. extractionBack-extract the aqueous layer
  8. dry with materialDry the combined organic layers with (anhydr Na2SO4)
  9. customrotary evaporate (40° C.)

出典と根拠

ORDレコード
ord-f7c105397eae445ba4ac9de7458efb82
出典データセット
uspto-grants-2007_10
特許番号
US07276516B2

反応ノート

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