Imidazole → HCID 57496388, compound

HRID 537742Notes

Reaction equation

HRID 537742 reaction equation
[F:1][C:2]1([F:30])[CH2:7][CH2:6][CH2:5][CH:4]([C@@H:8]2[CH2:13][C@H:12]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[CH2:11][CH2:10][N:9]2C(OCC2C=CC=CC=2)=O)[CH2:3]1.[H-].[Na+].N1C=CN=C1.C(=S)=S.IC.CC(N=NC(C#N)(C)C)(C#N)C.CCCC[SnH](CCCC)CCCC>C1COCC1.C1(C)C=CC=CC=1.O>[F:30][C:2]1([F:1])[CH2:7][CH2:6][CH2:5][CH:4]([C@@H:8]2[CH2:13][C@H:12]([C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=3)[CH2:11][CH2:10][NH:9]2)[CH2:3]1

Participants

11

Reactant 7

HCID 795ImidazoleHCID 5948TributylstannaneHCID 6328Methyl iodideHCID 6348Carbon DisulfideHCID 6547AzobisisobutyronitrileHCID 24758Sodium hydrideHCID 57496387HCID 57496387, compound

Product 1

HCID 57496388HCID 57496388, compoundYield 53%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 6 (647 mg, 2.9 mmol), NaH (232 mg, 5.8 mmol, 60% in mineral oil), imidazole (26 mg, 0.3 mmol) in THF (30 mL) was stirred for a half an hour at room temperature before CS2 (2 mL, 33.3 mmol) was introduced. After stirring for 1 h, iodomethane (0.3 mL, 4.8 mmol) was added. The resultant reaction mixture was stirred for another hour, poured into water (30 mL), extracted with EtOAc two times. The combined organic layers were washed with water and brine, dried over Na2SO4, filtered, and concentrated in vacuo to give a yellow oil. The residue was dissolved in toluene (30 mL), to which catalytic AIBN (100 mg) was added. The reaction mixture was refluxed under N2 while a solution of Bu3SnH (3 mL, 11 mmol) in toluene (3 mL) was added slowly over 30 minutes. After refluxing overnight, the reaction mixture was cooled, partitioned between saturated NaHCO3 aqueous solution and EtOAc. The combined organic layers were washed with water and brine, dried over Na2SO4. The solvent was removed in vacuo and the residue was purified by silica gel column (PE:EA=20:1) to afford 0.32 g of 7 (yield 53%).

Workup

  1. additionwas introduced
  2. customThe resultant reaction mixture
  3. stirringwas stirred for another hour
  4. extractionextracted with EtOAc two times
  5. washThe combined organic layers were washed with water and brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto give a yellow oil
  10. additionwas added
  11. additionwas added slowly over 30 minutes
  12. temperatureAfter refluxing overnight
  13. temperaturethe reaction mixture was cooled
  14. custompartitioned between saturated NaHCO3 aqueous solution and EtOAc
  15. washThe combined organic layers were washed with water and brine
  16. dry with materialdried over Na2SO4
  17. customThe solvent was removed in vacuo
  18. customthe residue was purified by silica gel column (PE:EA=20:1)

Sources & evidence

ORD record
ord-dd0fb8381ea34f7788d948c2c8f3991c
Source dataset
uspto-grants-2014_10
Patent number
US08865701B2

Reaction notes

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