Thiazole → HCID 22316611, compound

HRID 396756Notes

Reaction equation

HRID 396756 reaction equation
[S:1]1[CH:5]=[CH:4][N:3]=[CH:2]1.[Li]CCCC.[CH3:11][C:12]1[N:13]([C:27]2[CH:32]=[CH:31][C:30](Br)=[CH:29][CH:28]=2)[C:14]([C:17]2[CH:22]=[CH:21][C:20]([S:23]([CH3:26])(=[O:25])=[O:24])=[CH:19][CH:18]=2)=[CH:15][CH:16]=1>CCOCC.C1COCC1.[Cl-].[Zn+2].[Cl-].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:11][C:12]1[N:13]([C:27]2[CH:32]=[CH:31][C:30]([C:2]3[S:1][CH:5]=[CH:4][N:3]=3)=[CH:29][CH:28]=2)[C:14]([C:17]2[CH:18]=[CH:19][C:20]([S:23]([CH3:26])(=[O:25])=[O:24])=[CH:21][CH:22]=2)=[CH:15][CH:16]=1

Participants

8

Reactant 3

HCID 9256ThiazoleHCID 223168431-(4-Bromophenyl)-2-methyl-5-[4-(methylsulfonyl)phenyl]-1H-pyrroleHCID 178418339Butyllithium

Product 1

HCID 22316611HCID 22316611, compoundYield 13.2%

Reagents, catalysts & solvents 4

HCID 3007855ZincchlorideCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a stirred solution of thiazole (0.072 g, 0.85 mmol) in anhydrous ether (2 mL) was added n-BuLi (0.58 mL, 1.61 M solution in hexane, 0.94 mmol) at −78° C. under nitrogen, the mixture was stirred for 30 minutes at −78° C., and then zinc chloride (2.55 mL, 1.0 M solution in ether, 2.55 mmol) was added at −78° C., the mixture was stirred for 30 minutes at −78° C. The reaction mixture was warmed to 0° C., and added the solution of 2-methyl 5-[4-(methylsulfonyl)phenyl]-1-(4-bromophenyl)-1H-pyrrole (0.3 g, 0.77 mmol) in THF (5 mL), tetrakis(triphenylphosphine)palladium (0) (0.088 g, 0.08 mmol). The reaction mixture was heated at reflux temperature for 19 hours, and cooled down to room temperature. The reaction mixture was filtered through celite, the filtrate was poured into water and the whole was extracted with ethyl acetate (20 mL×3). The organic layer was washed with brine, dried over Na2SO4, and concentrated in vacuo. The residue was purified by flash chromatography eluting with hexane/ethyl acetate (2/1). The resulting solid was recrystallized from CH2Cl2/hexane to give the title compound (0.040 g, 13.2% yield).

Workup

  1. stirringthe mixture was stirred for 30 minutes at −78° C
  2. temperatureThe reaction mixture was warmed to 0° C.
  3. temperatureThe reaction mixture was heated
  4. temperatureat reflux temperature for 19 hours
  5. temperaturecooled down to room temperature
  6. filtrationThe reaction mixture was filtered through celite
  7. additionthe filtrate was poured into water
  8. extractionthe whole was extracted with ethyl acetate (20 mL×3)
  9. washThe organic layer was washed with brine
  10. dry with materialdried over Na2SO4
  11. concentrationconcentrated in vacuo
  12. customThe residue was purified by flash chromatography
  13. washeluting with hexane/ethyl acetate (2/1)
  14. customThe resulting solid was recrystallized from CH2Cl2/hexane

Sources & evidence

ORD record
ord-6832a0536b824499bd998ab57ab7b3b1
Source dataset
uspto-grants-2003_08
Patent number
US06608095B2

Reaction notes

Loading…