Isobutyric Acid → Ethyl 2-(4-isopropoxy-3-nitrophenyl)-4-methyl-5-thiazolecarboxylate

HRID 1051293Notes

Reaction equation

HRID 1051293 reaction equation
C(=O)([O-])O.[K+].Br[C:7]1[CH:12]=[CH:11][C:10]([O:13][CH:14]([CH3:16])[CH3:15])=[C:9]([N+:17]([O-:19])=[O:18])[CH:8]=1.[CH3:20][C:21]1[N:22]=[CH:23][S:24][C:25]=1[C:26]([O:28][CH2:29][CH3:30])=[O:27].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>[CH3:20][C:21]1[N:22]=[C:23]([C:7]2[CH:12]=[CH:11][C:10]([O:13][CH:14]([CH3:16])[CH3:15])=[C:9]([N+:17]([O-:19])=[O:18])[CH:8]=2)[S:24][C:25]=1[C:26]([O:28][CH2:29][CH3:30])=[O:27]

Participants

9

Reactant 5

HCID 6590Isobutyric AcidHCID 2986105-Thiazolecarboxylic acid, 4-methyl-, ethyl esterHCID 516893Potassium BicarbonateHCID 4643321Di-tert-butylcyclohexylphosphineHCID 222832414-Bromo-1-isopropoxy-2-nitrobenzene

Product 1

HCID 19965110Ethyl 2-(4-isopropoxy-3-nitrophenyl)-4-methyl-5-thiazolecarboxylateYield 66.1%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
120 °C

Procedure

A reaction mixture solution prepared by suspending 2.18 g of 4-bromo-2-nitrophenol and 2.07 g of potassium carbonate in 40 mL of dimethylformamide and adding 2.04 g of isopropyl iodide was heated under stirring at 110° C. for 14 hours under a nitrogen atmosphere. After the addition of water to the reaction mixture solution, extraction was performed using ethyl acetate. The organic layer was washed with saline, followed by drying and concentrating under reduced pressure. The resulting crude product was separated and purified by silica gel column chromatography to obtain 2.08 g of 4-bromo-2-nitro-1-(propan-2-yloxy)benzene. (2) A suspension was prepared by adding 1.05 g of potassium hydrogen carbonate, 22 mg of palladium chloride (II) and 102 mg of a copper bromide (I) dimethylsulfide complex to 2.08 g of 4-bromo-2-nitro-1-(propan-2-yloxy)benzene obtained above, followed by suspending the mixture in 15 mL of toluene. Subsequently, a reaction mixture solution prepared by adding 1.02 g of ethyl 4-methyl-1,3-thiazole-5-carboxylate, 46.2 μL of isobutyric acid and 114 mg of di-t-butylcyclohexylphosphine to the suspension was heated at 120° C. for 14 hours under a nitrogen atmosphere. The reaction mixture solution was celite-filtered to remove insoluble matter, water was added to the filtrate, extraction was performed using ethyl acetate. The organic layer was washed with saline and then dried and concentrated under reduced pressure, followed by purifying by a conventional method to obtain 1.38 g of ethyl 4-methyl-2-[3-nitro-4-(propan-2-yloxy)phenyl]-1,3-thiazole-5-carboxylate.

Workup

  1. customobtained above,
  2. customSubsequently, a reaction mixture solution prepared
  3. filtrationThe reaction mixture solution was celite-filtered
  4. customto remove insoluble matter, water
  5. additionwas added to the filtrate, extraction
  6. washThe organic layer was washed with saline
  7. customdried
  8. concentrationconcentrated under reduced pressure
  9. customby purifying by a conventional method

Sources & evidence

ORD record
ord-df55b1ac56d747c6ae1a557af93beb26
Source dataset
uspto-grants-2016_07
Patent number
US09388174B2

Reaction notes

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