Thioacetamide → Ethyl 2-methyl-4-(2-methylphenyl)-1,3-thiazole-5-carboxylate

HRID 474351Notes

Reaction equation

HRID 474351 reaction equation
[CH2:1]([O:3][C:4](=[O:16])[CH:5](Br)[C:6](=O)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[CH3:13])[CH3:2].[C:17]([NH2:20])(=[S:19])[CH3:18]>C(O)C>[CH2:1]([O:3][C:4]([C:5]1[S:19][C:17]([CH3:18])=[N:20][C:6]=1[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[CH3:13])=[O:16])[CH3:2]

Participants

4

Reactant 2

HCID 2723949ThioacetamideHCID 224373882-Bromo-3-oxo-3-o-tolyl-propionic acid ethyl ester

Product 1

HCID 53440888Ethyl 2-methyl-4-(2-methylphenyl)-1,3-thiazole-5-carboxylateYield 34%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A stirred mixture of 2-bromo-3-oxo-3-o-tolyl-propionic acid ethyl ester (2.74 g, 9.60 mmol, 1.0 equiv) and thioacetamide (0.76 g, 10.1 mmol, 1.05 equiv) in ethanol (30 mL) was heated to reflux for 4 hours. The cooled mixture was filtered and concentrated under vacuum. The residue was partitioned between ethyl acetate and water and the organic phase was separated and then washed with saturated aqueous sodium chloride solution. The collected organic was dried over magnesium sulphate, filtered, and concentrated under vacuum. The resultant residue was purified by flash column chromatography on silica gel (gradient: 0 to 20% ethyl acetate in pentane) to afford 0.84 g (34%) of 2-methyl-4-o-tolyl-thiazole-5-carboxylic acid ethyl ester as an oil. LCMS (ESI) m+H=261.9; 1H NMR (400 MHz, CDCl3) δ: 7.31-7.18 (m, 4H), 4.16 (q, 2H), 2.76 (s, 3H), 2.18 (s, 3H), 1.14 (t, 3H).

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 4 hours
  3. filtrationThe cooled mixture was filtered
  4. concentrationconcentrated under vacuum
  5. customThe residue was partitioned between ethyl acetate and water
  6. customthe organic phase was separated
  7. washwashed with saturated aqueous sodium chloride solution
  8. dry with materialThe collected organic was dried over magnesium sulphate
  9. filtrationfiltered
  10. concentrationconcentrated under vacuum
  11. customThe resultant residue was purified by flash column chromatography on silica gel (gradient: 0 to 20% ethyl acetate in pentane)

Sources & evidence

ORD record
ord-d8696266c6da46af8659fd8e3f03da8f
Source dataset
uspto-grants-2014_01
Patent number
US08637526B2

Reaction notes

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