Carbon Dioxide → HCID 57835218, compound

HRID 730629Notes

Reaction equation

HRID 730629 reaction equation
[Br:1][C:2]1[C:3]([CH3:14])=[CH:4][C:5]([O:12][CH3:13])=[C:6]([S:8]([NH2:11])(=[O:10])=[O:9])[CH:7]=1.CN(P(N(C)C)(N(C)C)=O)C.[Li+].CC([N-]C(C)C)C.[C:34](=[O:36])=[O:35]>C1COCC1>[Br:1][C:2]1[CH:7]=[C:6]([S:8](=[O:10])(=[O:9])[NH2:11])[C:5]([O:12][CH3:13])=[CH:4][C:3]=1[CH2:14][C:34]([OH:36])=[O:35]

Participants

6

Reactant 4

HCID 280Carbon DioxideHCID 12679HexamethylphosphoramideHCID 2724682Lithium diisopropylamideHCID 215206975-Bromo-2-methoxy-4-methylbenzenesulfonamide

Product 1

HCID 57835218HCID 57835218, compoundYield 3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-75 °C

Procedure

A dry 25 mL 3-neck RBF, fitted with a magnetic stirring bar, a thermometer and septum with Ar inlet was charged with 5-bromo-2-methoxy-4-methylbenzene-sulfonamide 12e (0.586 g, 2.1 mmol), anhydrous THF (5 mL) and HMPA (0.37 mL, 2.1 mmol). The mixture was cooled to −75° C. and a 2.0 M solution of LDA (4.2 mL, 8.4 mmol) was added drop wise via a syringe. The reaction mixture was stirred at −75° C. for 1.5 hours and then cannulated into a flask containing 20 g of dry ice and 5 mL THF and left to warm up slowly to RT. The solvent was removed under reduced pressure and H2O (20 mL) was added to the residue. At this point, some of the unreacted starting material precipitated and was removed by filtration. The filtrate was acidified and the solution was extracted with EtOAc (3×20 mL). The combined organic layers were evaporated to dryness, the residue was treated with an aqueous solution of saturated NaHCO3 (10 mL) and the insoluble material was separated by filtration. The filtrate was acidified with concentrated HCl and the cloudy solution extracted again with EtOAc (3×5 mL). The combined organic layers were concentrated to ˜1 mL, causing crystallization of the product, which was collected by filtration to give pure (2-bromo-5-methoxy-4-sulfamoylphenyl)acetic acid (20 mg) 12f (˜3% yield).

Workup

  1. customA dry 25 mL 3-neck RBF, fitted with a magnetic stirring bar
  2. customcannulated into a flask
  3. waitleft
  4. temperatureto warm up slowly to RT
  5. customThe solvent was removed under reduced pressure and H2O (20 mL)
  6. additionwas added to the residue
  7. customprecipitated
  8. customwas removed by filtration
  9. extractionthe solution was extracted with EtOAc (3×20 mL)
  10. customThe combined organic layers were evaporated to dryness
  11. additionthe residue was treated with an aqueous solution of saturated NaHCO3 (10 mL)
  12. customthe insoluble material was separated by filtration
  13. extractionthe cloudy solution extracted again with EtOAc (3×5 mL)
  14. concentrationThe combined organic layers were concentrated to ˜1 mL
  15. customcrystallization of the product, which
  16. filtrationwas collected by filtration

Sources & evidence

ORD record
ord-e2e9644bbea94bae982a3e1c3f39a3bb
Source dataset
uspto-grants-2009_09
Patent number
US07582766B2

Reaction notes

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