2-Bromothiazole → HCID 23510389, compound

HRID 1883200Notes

Reaction equation

HRID 1883200 reaction equation
Br[C:2]1[S:3][CH:4]=[CH:5][N:6]=1.[Li]CCCC.I[C:13]1[CH:23]=[CH:22][C:16]([C:17]([O:19][CH2:20][CH3:21])=[O:18])=[CH:15][CH:14]=1.O.O.[Na+].[Na+].C(N(CC(O)=O)CC(O)=O)CN(CC([O-])=O)CC([O-])=O.C(=O)([O-])O.[Na+]>CCOCC.CCCCCC.[Cl-].[Cl-].[Zn+2].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.C1COCC1>[S:3]1[CH:4]=[CH:5][N:6]=[C:2]1[C:13]1[CH:23]=[CH:22][C:16]([C:17]([O:19][CH2:20][CH3:21])=[O:18])=[CH:15][CH:14]=1

Participants

11

Reactant 5

HCID 764302-BromothiazoleHCID 142891Ethyl 4-iodobenzoateHCID 516892Sodium BicarbonateHCID 44120005Edta disodiumHCID 178418339Butyllithium

Product 1

HCID 23510389HCID 23510389, compoundYield 71%

Reagents, catalysts & solvents 5

HCID 3007855ZincchlorideCatalyst2×HCID 178418397HCID 178418397, compoundCatalystHCID 3283Diethyl EtherSolvent3×HCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent

Conditions

Temperature
-78 °C

Procedure

Under nitrogen atmosphere, a solution of 2-bromothiazole (2.00 g) in Et2O (38 mL) was cooled to −78° C., and thereto was added a 1.5N solution of n-BuLi in hexane (8.5 mL), and the mixture was stirred at −78° C. for 30 minutes. To the mixture was added a 1.0N solution of ZnCl2 in Et2O (12.2 mL), and the mixture was stirred at −78° C. for 10 minutes, and stirred at room temperature for 30 minutes. To the mixture were added successively Pd(PPh3)4 (704 mg) and ethyl 4-iodobenzoate (2.26 g), and the mixture was stirred at 66° C. for 1 hour. To the mixture was added a 1.0N solution of ZnCl2 in Et2O (12.2 mL), and the mixture was stirred at 66° C. for 2 hours. To the mixture was added THF (60 mL), and the mixture was stirred at 66° C. for 2.5 hours. To the mixture were added a 0.18N aqueous solution of ethylene-diaminetetraacetic acid disodium salt dihydrate (300 mL), and sodium hydrogen carbonate until the pH value of the mixture became pH=8. The mixture was extracted with ethyl acetate, washed with an aqueous NaHSO3 solution, and dried over MgSO4. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column (hexane/ethyl acetate=12.5/1) to give ethyl 4-(1,3-thiazol-2-yl)benzoate (1.35 g, 71%).

Workup

  1. stirringthe mixture was stirred at −78° C. for 10 minutes
  2. stirringstirred at room temperature for 30 minutes
  3. stirringthe mixture was stirred at 66° C. for 1 hour
  4. stirringthe mixture was stirred at 66° C. for 2 hours
  5. stirringthe mixture was stirred at 66° C. for 2.5 hours
  6. extractionThe mixture was extracted with ethyl acetate
  7. washwashed with an aqueous NaHSO3 solution
  8. dry with materialdried over MgSO4
  9. customThe solvent was evaporated under reduced pressure
  10. customthe residue was purified by silica gel column (hexane/ethyl acetate=12.5/1)

Sources & evidence

ORD record
ord-a4f76778a64242408b00d1cad7a14495
Source dataset
uspto-grants-2004_07
Patent number
US06759429B2

Reaction notes

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