Thiobenzamide → 4-Methoxymethyl-2-phenyl-thiazole-5-carboxylic acid methyl ester

HRID 396386Notes

Reaction equation

HRID 396386 reaction equation
[CH3:1][O:2][C:3]([CH:5]([C:7]([CH2:9][O:10][CH3:11])=O)Cl)=[O:4].[C:12]([NH2:20])(=[S:19])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1>CCO>[CH3:1][O:2][C:3]([C:5]1[S:19][C:12]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[N:20][C:7]=1[CH2:9][O:10][CH3:11])=[O:4]

Participants

4

Reactant 2

HCID 683563ThiobenzamideHCID 59295416Methyl 2-chloro-4-methoxy-3-oxobutanoate

Product 1

HCID 99651204-Methoxymethyl-2-phenyl-thiazole-5-carboxylic acid methyl esterYield 47%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A solution of CH3O2CCH(Cl)COCH2OCH3 (68 mmole, 1.2 eq), prepared according to De Kimpe et al., Synthesis, 188 (1986), in absolute EtOH (75 ml) was treated with thiobenzamide (7.8 g, 56.7 mmole, 1.0 eq) and the resulting brown mixture refluxed under nitrogen for 8 hours. The mixture was partitioned between ethyl acetate and saturated NaHCO3. The organic layer was washed with water twice and brine, then dried over anhydrous sodium sulfate and concentrated in vacuo to give a brown oil. Silica gel chromatography eluting with (9:1) hexanes-ethyl acetate provided 6.98 g (47%) of title compound as a yellow crystalline solid. 1H NMR (CDCl3): δ 3.6 (s, 3H), 3.9 (s, 3H), 4.95 (s, 2H), 7.4-7.5 (m, 3H), 8.0 (m, 2H).

Workup

  1. temperaturethe resulting brown mixture refluxed under nitrogen for 8 hours
  2. customThe mixture was partitioned between ethyl acetate and saturated NaHCO3
  3. washThe organic layer was washed with water twice
  4. dry with materialbrine, then dried over anhydrous sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customto give a brown oil
  7. washSilica gel chromatography eluting with (9:1) hexanes-ethyl acetate

Sources & evidence

ORD record
ord-e87c70b011f9490885af3bd1b057cb0f
Source dataset
uspto-grants-2003_08
Patent number
US06608087B1

Reaction notes

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