Hydrochloric Acid → Ethyl 2-(3-chloro-4-hydroxyphenyl)-4-methyl-5-thiazolecarboxylate

HRID 977104Notes

Reaction equation

HRID 977104 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:9][C:10]([C:14]([O:16][CH2:17][CH3:18])=[O:15])=[C:11]([CH3:13])[N:12]=2)=[CH:4][C:3]=1[N+]([O-])=O.[ClH:22].CO.O>C(O)C.C(OCC)(=O)C.[Pd]>[Cl:22][C:3]1[CH:4]=[C:5]([C:8]2[S:9][C:10]([C:14]([O:16][CH2:17][CH3:18])=[O:15])=[C:11]([CH3:13])[N:12]=2)[CH:6]=[CH:7][C:2]=1[OH:1]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 887MethanolHCID 962WaterHCID 135737466Ethyl 2-(4-hydroxy-3-nitrophenyl)-4-methylthiazole-5-carboxylate

Product 1

HCID 135737470Ethyl 2-(3-chloro-4-hydroxyphenyl)-4-methyl-5-thiazolecarboxylateYield 91%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 702EthanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

5.0 g of Ethyl 2-(4-hydroxy-3-nitrophenyl)-4-methyl-5-thiazolecarboxylate was dissolved in 120 ml of ethanol and 60 ml of ethyl acetate, and 2 ml of concentrated hydrochloride and 500 mg of a 10% palladium/carbon was added thereto, and the mixture was stirred under a hydrogen atmosphere for 24 hours. After the completion of the reaction, methanol and water were added thereto, the mixture was filtered, and the filtrate was concentrated. The resulting crystal was suspended in 25 ml of 2N hydrochloric acid and 25 ml of acetone, and a solution of 1.2 g of sodium nitrite in 8 ml of water was gradually added thereto with ice cooling. Separately, 2.2 g of cuprous chloride was suspended in 15 ml of 2N hydrochloric acid and the diazonium salt solution was gradually added thereto with ice cooling. After the completion of the dropwise addition, the reaction mixture was heated to 60° C., and one hour after the heating, 100 ml of water was added thereto. The precipitated crystal was collected by filtration. This product was purified by silica gel chromatography to give 4.4 g of ethyl 2-(3-chloro-4-hydroxyphenyl)-4-methyl-5-thiazolecarboxylate (yield: 91%).

Workup

  1. additionwere added
  2. filtrationthe mixture was filtered
  3. concentrationthe filtrate was concentrated
  4. addition25 ml of acetone, and a solution of 1.2 g of sodium nitrite in 8 ml of water was gradually added
  5. additionthe diazonium salt solution was gradually added
  6. additionAfter the completion of the dropwise addition
  7. additionone hour after the heating, 100 ml of water was added
  8. filtrationThe precipitated crystal was collected by filtration
  9. customThis product was purified by silica gel chromatography

Sources & evidence

ORD record
ord-4cad15396de3422eb846a25c36a8285e
Source dataset
uspto-grants-1997_03
Patent number
US05614520

Reaction notes

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