Chloroacetone → Ethyl 2-(4-methyl-1,3-thiazol-2-yl)propanoate

HRID 522621Notes

Reaction equation

HRID 522621 reaction equation
[NH2:1][C:2](=[S:10])[CH:3]([CH3:9])[C:4]([O:6][CH2:7][CH3:8])=[O:5].Cl[CH2:12][C:13](=O)[CH3:14].C([O-])(O)=O.[Na+]>CN(C=O)C>[CH3:14][C:13]1[N:1]=[C:2]([CH:3]([CH3:9])[C:4]([O:6][CH2:7][CH3:8])=[O:5])[S:10][CH:12]=1

Participants

5

Reactant 3

HCID 6571ChloroacetoneHCID 516892Sodium BicarbonateHCID 11819343Ethyl 2-carbamothioyl-2-methylacetate

Product 1

HCID 66751996Ethyl 2-(4-methyl-1,3-thiazol-2-yl)propanoateYield 93%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of Intermediate 103 (6.6 g, 40.9 mmol) and chloroacetone (FLUKA, 3.27 mL, 40.9 mmol) in DMF (50 mL) was stirred at 80° C. for 5 h. Reaction mixture was cooled to room temperature, treated with NaHCO3 (150 mL) and extracted with ethyl ether (2×200 mL). Organic layer was washed with brine, dried over Na2SO4 and evaporated to give title compound (7.57 g, 38.0 mmol, 93% yield) as yellow oil. 1H NMR (300 MHz, DMSO-d6) δ ppm: 7.19 (s, 1H), 4.23-4.06 (m, 3H), 2.31 (s, 3H), 1.48 (d, 3H), 1.16 (t, 3H). [ES+MS] m/z 200 (MH+). It was subsequently observed that this compound undergoes autooxidation at the stereogenic centre to form ethyl 2-hydroxy-2-(4-methyl-1,3-thiazol-2-yl)propanoate. Once the presence of this compound had been observed, the compound was actively synthesised, hereinbelow described as Intermediate 106.

Workup

  1. customReaction mixture
  2. temperaturewas cooled to room temperature
  3. extractionextracted with ethyl ether (2×200 mL)
  4. washOrganic layer was washed with brine
  5. dry with materialdried over Na2SO4
  6. customevaporated

Sources & evidence

ORD record
ord-cc6ea97da4384857ac1fdc6c63567309
Source dataset
uspto-grants-2016_05
Patent number
US09334265B2

Reaction notes

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