Hydrochloric Acid → Ethyl 2-Chloro-4-Ethyl-5-Thiazolecarboxylate

HRID 279746Notes

Reaction equation

HRID 279746 reaction equation
N[C:2]1[S:3][C:4]([C:9]([O:11][CH2:12][CH3:13])=[O:10])=[C:5]([CH2:7][CH3:8])[N:6]=1.[ClH:14].N([O-])=O.[Na+]>O>[Cl:14][C:2]1[S:3][C:4]([C:9]([O:11][CH2:12][CH3:13])=[O:10])=[C:5]([CH2:7][CH3:8])[N:6]=1

Participants

5

Reactant 3

HCID 313Hydrochloric Acid2×HCID 12801682Ethyl 2-amino-4-ethyl-1,3-thiazole-5-carboxylateHCID 23668193Sodium Nitrite

Product 1

HCID 13282757Ethyl 2-Chloro-4-Ethyl-5-Thiazolecarboxylate

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Ethyl 2-chloro 3-oxo-pentanoate is prepared from ethyl 3-oxo-pentanoate and sulfuryl chloride utilizing the procedure of Bankowski et al, Rocz. Chem., Volume 49, Page 1899 (1971). A mixture of 9.2 g (0.0515 mole) of ethyl 2-chloro 3-oxo-pentanoate, 3.92 g (0.0515 mole) of thiourea and 30 ml. of ethanol was held at reflux for 17 hours. Ethanol was removed under reduced pressure and the residue was treated with 300 ml. of saturated sodium bicarbonate solution. The solid precipitate was collected to give 11.2 g of white solid, m.p. 165°-170° C. which was recrystallized from ethanol to give 7.7 g (75%) of ethyl 2-amino-4-ethyl-5-thiazolecarboxylate as colorless prisms, m.p. 177°-179° C. To a solution of 7.0 g (0.0349 mole) of ethyl 2-amino-4-ethyl-5-thiazolecarboxylate and 0.2 g of CaSO 4 in 60 ml. of concentrated HCl was added dropwise a solution of NaNO2 in 20 ml. of water in such a way that the reaction temperature did not exceed 30° C. The reaction mixture was stirred for 30 minutes and poured into a solution of 3.5 g (0.035 mole) of cuprous chloride in 30 ml. of 6N HCl. The resulting dark blue solution was stirred for 30 minutes and extracted with ether. The ether solution was dried and concentrated under reduced pressure. The residue was Kugelrohr distilled at 2 mm. to give 4.35 g of yellow liquid which was chromatographed on silica gel to give 4.0 g (52%) of the desired product as colorless liquid, nD25 =1.5189.

Workup

  1. customdid not exceed 30° C
  2. stirringThe resulting dark blue solution was stirred for 30 minutes
  3. extractionextracted with ether
  4. dry with materialThe ether solution was dried
  5. concentrationconcentrated under reduced pressure
  6. distillationdistilled at 2 mm

Sources & evidence

ORD record
ord-7b920606ca7b4414865d3dcae0d5c8e8
Source dataset
uspto-grants-1986_05
Patent number
US04586948

Reaction notes

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