Thiourea → 5-Thiazolecarboxylic acid, 2-amino-4-(trifluoromethyl)-, ethyl ester

HRID 917297Notes

Reaction equation

HRID 917297 reaction equation
Cl[CH:2]([C:8]([C:10]([F:13])([F:12])[F:11])=O)[C:3]([O:5][CH2:6][CH3:7])=[O:4].[NH2:14][C:15]([NH2:17])=[S:16]>C(O)C>[CH2:6]([O:5][C:3]([C:2]1[S:16][C:15]([NH2:17])=[N:14][C:8]=1[C:10]([F:13])([F:12])[F:11])=[O:4])[CH3:7]

Participants

4

Reactant 2

HCID 2723790ThioureaHCID 2737165Ethyl 2-chloro-4,4,4-trifluoro-3-oxobutanoate

Product 1

HCID 676565-Thiazolecarboxylic acid, 2-amino-4-(trifluoromethyl)-, ethyl esterYield 75.4%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of ethyl 2-chloro-4,4,4-trifluoroacetoacetate (50.0 g, 230 mmol) in ethanol (250 mL) was added thiourea (17.5 g, 230 mmol). The resulting mixture was heated at reflux for 3 h, at which time TLC indicated a complete reaction. The mixture was concentrated in vacuo, and the residue dissolved in ether. The organic layer was successively washed with aqueous sodium bicarbonate, and brine, then dried over magnesium sulfate and concentrated in vacuo. The resulting solid was recrystalized with ethyl acetate and hexanes to give white crystals (41.64 g, 75% yield). 1H NMR (MeOD-d4, 300 MHz): δ 4.26 (q, J=7.1 Hz, 2H), 1.31 (t, J=7.1 Hz, 3H).

Workup

  1. temperatureThe resulting mixture was heated
  2. temperatureat reflux for 3 h, at which time TLC
  3. customa complete reaction
  4. concentrationThe mixture was concentrated in vacuo
  5. dissolutionthe residue dissolved in ether
  6. washThe organic layer was successively washed with aqueous sodium bicarbonate, and brine
  7. dry with materialdried over magnesium sulfate
  8. concentrationconcentrated in vacuo
  9. customThe resulting solid was recrystalized with ethyl acetate and hexanes

Sources & evidence

ORD record
ord-2036f1a81cac4d0c9a88226ed22ba859
Source dataset
uspto-grants-2007_09
Patent number
US07273866B2

Reaction notes

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