Tetrahydrofuran → HCID 22049707, compound

HRID 1830867Notes

Reaction equation

HRID 1830867 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[C:10](Br)[S:11][CH:12]=2)=[CH:4][CH:3]=1.Br[C:15]1[CH:16]=[N:17][CH:18]=[C:19]([CH:25]=1)[C:20]([O:22]CC)=[O:21].O1CC[CH2:28][CH2:27]1>[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>[CH2:27]([C:18]1[N:17]=[CH:16][C:15]([C:10]2[S:11][CH:12]=[C:8]([C:5]3[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=3)[N:9]=2)=[CH:25][C:19]=1[C:20]([OH:22])=[O:21])[CH3:28]

Participants

6

Reactant 3

HCID 8028Tetrahydrofuran2×HCID 140785Ethyl 5-bromopyridine-3-carboxylateHCID 220497472-Bromo-4-(4-chlorophenyl)-1,3-thiazole

Product 1

HCID 22049707HCID 22049707, compoundYield 51%

Reagents, catalysts & solvents 2

HCID 3007855ZincchlorideCatalystHCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
-78 °C

Procedure

A solution of compound (41) (0.25 g, 0.91 mmol) in tetrahydrofuran (5 ml) was cooled to −78° C. under an argon atmosphere and 1.6 M n-butyllithium-hexane solution (0.57 ml, 0.91 mmol) was added. After stirring at −78° C. for 30 min., a solution of zinc chloride (0.12 g, 0.91 mmol) in tetrahydrofuran (2 ml) was added to the reaction mixture. The reaction mixture was warmed to room temperature and stirred for 30 min. and ethyl 5-bromonicotinate (0.21 g, 0.91 mmol) and tetrakis(triphenylphosphine)palladium (0.16 g, 0.14 mmol) were added. The mixture was heated to 75° C. and stirred for 2 hrs. After cooling, the reaction mixture was poured into ice water and partitioned between ethyl acetate and brine. The aqueous layer was extracted with ethyl acetate and the extracts were combined and dried (MgSO4), and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography, and crystallized from ethyl acetate-n-hexane to give white crystals (0.16 g, 51%).

Workup

  1. addition1.6 M n-butyllithium-hexane solution (0.57 ml, 0.91 mmol) was added
  2. temperatureThe reaction mixture was warmed to room temperature
  3. stirringstirred for 30 min.
  4. temperatureThe mixture was heated to 75° C.
  5. stirringstirred for 2 hrs
  6. temperatureAfter cooling
  7. custompartitioned between ethyl acetate and brine
  8. extractionThe aqueous layer was extracted with ethyl acetate
  9. dry with materialdried (MgSO4)
  10. customthe solvent was evaporated under reduced pressure
  11. customThe obtained residue was purified by silica gel column chromatography
  12. customcrystallized from ethyl acetate-n-hexane

Sources & evidence

ORD record
ord-a3de0a11f79645059b0888b511d5f4cc
Source dataset
uspto-grants-2006_06
Patent number
US07067537B2

Reaction notes

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