Ethyl 2-chloroacetoacetate → Ethyl 2-amino-4-methylthiazole-5-carboxylate

HRID 1870492Notes

Reaction equation

HRID 1870492 reaction equation
Cl[CH:2]([C:8]([CH3:10])=O)[C:3]([O:5][CH2:6][CH3:7])=[O:4].[NH2:11][C:12]([NH2:14])=[S:13]>C(O)C>[NH2:14][C:12]1[S:13][C:2]([C:3]([O:5][CH2:6][CH3:7])=[O:4])=[C:8]([CH3:10])[N:11]=1

Participants

4

Reactant 2

HCID 11858Ethyl 2-chloroacetoacetateHCID 2723790Thiourea

Product 1

HCID 343747Ethyl 2-amino-4-methylthiazole-5-carboxylateYield 98%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of ethyl 2-chloroacetoacetate (50 g, 0.30 mol, Aldrich) and thiourea (45.6 g, 0.60 mol) in 400 mL of absolute ethanol was heated to reflux. After refluxing overnight the reaction mixture was allowed to cool to room temperature and then concentrated to half the original volume in vacuo. The remaining ethanol solution was poured into H2O (1L) and made basic (pH 10) with 2N NaOH. An off-white solid precipitated immediately. The mixture was stirred for ~10 minutes and then the solid was removed by vacuum filtration and dried to give 54.75 g (98% yield) of the desired product as a white solid: 1H NMR (CDCl3) 67 5.5 (bs, 2H), 4.25 (q, 2H), 2.5 (s, 3H), 1.35 (t, 3H).

Workup

  1. temperaturewas heated to reflux
  2. temperatureAfter refluxing overnight the reaction mixture
  3. concentrationconcentrated to half the original volume in vacuo
  4. additionThe remaining ethanol solution was poured into H2O (1L)
  5. customAn off-white solid precipitated immediately
  6. customthe solid was removed by vacuum filtration
  7. customdried

Sources & evidence

ORD record
ord-fde23cc8ab75469e90fd039b4fed362e
Source dataset
uspto-grants-2000_08
Patent number
US06096898

Reaction notes

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