Isobutyric Acid → Ethyl 2-(4-fluoro-3-nitrophenyl)-4-methyl-1,3-thiazole-5-carboxylate

HRID 1051304Notes

Reaction equation

HRID 1051304 reaction equation
C(=O)([O-])O.[K+].Br[C:7]1[CH:8]=[CH:9][C:10]([F:16])=[C:11]([N+:13]([O-:15])=[O:14])[CH:12]=1.[CH3:17][C:18]1[N:19]=[CH:20][S:21][C:22]=1[C:23]([O:25][CH2:26][CH3:27])=[O:24].C(O)(=O)C(C)C.C(P(C(C)(C)C)C1CCCCC1)(C)(C)C>C1(C)C=CC=CC=1.Cl[Pd]Cl.[Cu](Br)Br>[F:16][C:10]1[CH:9]=[CH:8][C:7]([C:20]2[S:21][C:22]([C:23]([O:25][CH2:26][CH3:27])=[O:24])=[C:18]([CH3:17])[N:19]=2)=[CH:12][C:11]=1[N+:13]([O-:15])=[O:14]

Participants

9

Reactant 5

HCID 6590Isobutyric AcidHCID 2986105-Thiazolecarboxylic acid, 4-methyl-, ethyl esterHCID 516893Potassium BicarbonateHCID 27363284-Bromo-1-fluoro-2-nitrobenzeneHCID 4643321Di-tert-butylcyclohexylphosphine

Product 1

HCID 118555037Ethyl 2-(4-fluoro-3-nitrophenyl)-4-methyl-1,3-thiazole-5-carboxylateYield 73.5%

Reagents, catalysts & solvents 3

HCID 24290Palladium ChlorideCatalystHCID 24611Copper bromide (CuBr2)CatalystHCID 1140TolueneSolvent

Conditions

Temperature
120 °C

Procedure

A mixture was prepared by adding 2.10 g of potassium hydrogen carbonate, 44 mg of palladium chloride (II) and 205 mg of a copper bromide (I) dimethylsulfide complex to 2.20 g of 5-bromo-2-fluoronitrobenzene and the resulting mixture was suspended in 20 mL of toluene. Subsequently, a reaction mixture solution prepared by adding 2.05 g of ethyl 4-methyl-1,3-thiazole-5-carboxylate, 92.5 μL of isobutyric acid and 228 mg of di-t-butylcyclohexylphosphine to the resulting suspension was heated at 120° C. for 14 hours under a nitrogen atmosphere. The reaction mixture solution was celite-filtered to remove insoluble matter and water was added to the filtrate, and extraction was performed using ethyl acetate. The organic layer was washed with saline and dried and concentrated under reduced pressure. The resulting crude product was separated and purified by silica gel column chromatography to obtain 2.28 g of ethyl 2-(4-fluoro-3-nitrophenyl)-4-methyl-1,3-thiazole-5-carboxylate.

Workup

  1. customA mixture was prepared
  2. customSubsequently, a reaction mixture solution prepared
  3. filtrationThe reaction mixture solution was celite-filtered
  4. customto remove insoluble matter and water
  5. additionwas added to the filtrate, and extraction
  6. washThe organic layer was washed with saline
  7. customdried
  8. concentrationconcentrated under reduced pressure
  9. customThe resulting crude product was separated
  10. custompurified by silica gel column chromatography

Sources & evidence

ORD record
ord-d31b808f8970403682c7aaac07b92084
Source dataset
uspto-grants-2016_07
Patent number
US09388174B2

Reaction notes

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