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

HRID 1178921Notes

Reaction equation

HRID 1178921 reaction equation
[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

Participants

6

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

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).

Workup

  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.)

Sources & evidence

ORD record
ord-f7c105397eae445ba4ac9de7458efb82
Source dataset
uspto-grants-2007_10
Patent number
US07276516B2

Reaction notes

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