Hydrochloric Acid → HCID 10216985, compound

HRID 2250538Notes

Reaction equation

HRID 2250538 reaction equation
C([CH:3]([CH:7]1[C:19]2[N:18]([CH2:20][C:21]3[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][CH:22]=3)[C:17]3[C:12](=[CH:13][C:14]([F:29])=[CH:15][C:16]=3Br)[C:11]=2[CH2:10][CH2:9][CH2:8]1)[C:4]([O-:6])=[O:5])C.[Na+].[CH3:31][S:32]([O-:34])=[O:33].[OH-].[Na+].Cl>CN1C(=O)CCC1.C1COCC1.[Cu]I.CO>[Cl:27][C:24]1[CH:23]=[CH:22][C:21]([CH2:20][N:18]2[C:19]3[CH:7]([CH2:3][C:4]([OH:6])=[O:5])[CH2:8][CH2:9][CH2:10][C:11]=3[C:12]3[C:17]2=[C:16]([S:32]([CH3:31])(=[O:34])=[O:33])[CH:15]=[C:14]([F:29])[CH:13]=3)=[CH:26][CH:25]=1

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 2733271Sodium methanesulfinateHCID 131726735HCID 131726735, compound

Product 1

HCID 10216985HCID 10216985, compoundYield 61.8%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 887MethanolSolventHCID 8028TetrahydrofuranSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
140 °C

Procedure

To a solution of 478 mg of the ester prepared in step 2 in 8 mL of NMP, 510 mg of methanesulfinic acid sodium salt and 950 mg of CuI (I) was added successively. The resulting mixture was degassed under a flow of N2, then heated at 140° C. for 8 h under rigorous stirring. The reaction mixture was cooled to room temperature, diluted with minimum amount of a 1:1 mixture of EtOAc/hexane. The resulting mixture was filtered through a pad of silica gel, further eluted with EtOAc. The filtrate was concentrated to about 50 mL, and washed with water and brine. The organic phase was collected, dried over anhydrous sodium sulfate, filtered, and evaporated. The residue was purified by flash chromatography over silica gel (30% EtOAc/hexane) to afford 320 mg of desired sulfonated material, which was dissolved in 5 mL of THF plus 5 mL of methanol. To the resulting solution, 5 mL of 2 N of NaOH was added and the resulting mixture was stirred at rt for 6 h. The reaction mixture was neutralized with 1 M HCl aqueous solution and extracted with EtOAc. The separated organic phase was dried over anhydrous sodium sulfate, filtered, and evaporated. The residue was refluxed with hexane under rigorous stirring for 0.5 h. The resulting mixture was cooled to rt under rigorous stirring, and filtered to afford 278 mg of desired acid.

Workup

  1. customThe resulting mixture was degassed under a flow of N2
  2. temperatureThe reaction mixture was cooled to room temperature
  3. additiondiluted with minimum amount of a 1:1 mixture of EtOAc/hexane
  4. filtrationThe resulting mixture was filtered through a pad of silica gel
  5. washfurther eluted with EtOAc
  6. concentrationThe filtrate was concentrated to about 50 mL
  7. washwashed with water and brine
  8. customThe organic phase was collected
  9. dry with materialdried over anhydrous sodium sulfate
  10. filtrationfiltered
  11. customevaporated
  12. customThe residue was purified by flash chromatography over silica gel (30% EtOAc/hexane)
  13. customto afford 320 mg
  14. extractionextracted with EtOAc
  15. dry with materialThe separated organic phase was dried over anhydrous sodium sulfate
  16. filtrationfiltered
  17. customevaporated
  18. temperatureThe residue was refluxed with hexane
  19. stirringunder rigorous stirring for 0.5 h
  20. temperatureThe resulting mixture was cooled to rt under rigorous stirring
  21. filtrationfiltered

Sources & evidence

ORD record
ord-6db3ce52cd604d6191ae723d4b19c209
Source dataset
uspto-grants-2008_01
Patent number
US07317036B2

Reaction notes

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