Sodium Carbonate → 2-{4-[3-(2,6-Dichloro-phenyl)-5-isopropyl-isoxazol-4-ylmethoxy]-2-methyl-phenyl}-benzo[b]thiophene-4-carboxylic acid

HRID 250290Notes

Reaction equation

HRID 250290 reaction equation
Br[C:2]1[CH:25]=[CH:24][C:5]([O:6][CH2:7][C:8]2[C:9]([C:16]3[C:21]([Cl:22])=[CH:20][CH:19]=[CH:18][C:17]=3[Cl:23])=[N:10][O:11][C:12]=2[CH:13]([CH3:15])[CH3:14])=[CH:4][C:3]=1[CH3:26].C(=O)([O-])[O-].[Na+].[Na+].[C:33]([C:36]1[C:44]2[CH:43]=[C:42](B(O)O)[S:41][C:40]=2[CH:39]=[CH:38][CH:37]=1)([OH:35])=[O:34]>O1CCOCC1>[Cl:23][C:17]1[CH:18]=[CH:19][CH:20]=[C:21]([Cl:22])[C:16]=1[C:9]1[C:8]([CH2:7][O:6][C:5]2[CH:24]=[CH:25][C:2]([C:42]3[S:41][C:40]4[CH:39]=[CH:38][CH:37]=[C:36]([C:33]([OH:35])=[O:34])[C:44]=4[CH:43]=3)=[C:3]([CH3:26])[CH:4]=2)=[C:12]([CH:13]([CH3:15])[CH3:14])[O:11][N:10]=1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 672722084-(4-Bromo-3-methyl-phenoxymethyl)-3-(2,6-dichloro-phenyl)-5-isopropyl-isoxazoleHCID 67272237(4-Carboxybenzo[b]thiophen-2-yl)boronic acid

Product 1

HCID 580883582-{4-[3-(2,6-Dichloro-phenyl)-5-isopropyl-isoxazol-4-ylmethoxy]-2-methyl-phenyl}-benzo[b]thiophene-4-carboxylic acidYield 27.2%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

To a 60° C. suspension of 4-(4-Bromo-3-methyl-phenoxymethyl)-3-(2,6-dichloro-phenyl)-5-isopropyl-isoxazole (0.90 mmol; 410 mg) in a 2M solution of sodium carbonate (7.20 mmol; 3.6 mL) and 1.5 mL of deoxygenated dioxane under a nitrogen atmosphere is slowly added a solution of 4-carboxy-benzo[b]thiophen-2-boronic acid (1.08=mol; 240 mg) in 3.5 mL of deoxygenated dioxane over 1 h via an addition pump. The mixture is stirred for 1 h. The organic solvent is removed under reduced pressure and the residue is acidified with 1N HCl to pH 4. The resulting solution is extracted with dichloromethane. The organic layers are combined, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue is chromatographed using a gradient from 100% dichloromethane to 100% ethyl acetate to obtain a solid which is washed with acetonitrile to yield the title compound (135 mg, 27%) as a white solid.

Workup

  1. customThe organic solvent is removed under reduced pressure
  2. extractionThe resulting solution is extracted with dichloromethane
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue is chromatographed
  7. customto obtain a solid which
  8. washis washed with acetonitrile

Sources & evidence

ORD record
ord-90bd45e48c0c4cf4ad9d94224a9ffda6
Source dataset
uspto-grants-2011_01
Patent number
US07863302B2

Reaction notes

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