Sulfuric Acid → Methyl 2-chloro-5-ethylthiazole-4-carboxylate

HRID 2402882Notes

Reaction equation

HRID 2402882 reaction equation
N([O-])=O.[Na+].N[C:6]1[S:7][C:8]([CH2:15][CH3:16])=[C:9]([C:11]([O:13][CH3:14])=[O:12])[N:10]=1.[Na+].[Cl-:18].OS(O)(=O)=O>O.[Cl-].[Na+].O.Cl[Cu]>[Cl:18][C:6]1[S:7][C:8]([CH2:15][CH3:16])=[C:9]([C:11]([O:13][CH3:14])=[O:12])[N:10]=1

Participants

8

Reactant 4

HCID 1118Sulfuric AcidHCID 5234Sodium ChlorideHCID 737585Methyl 2-amino-5-ethyl-1,3-thiazole-4-carboxylateHCID 23668193Sodium Nitrite

Product 1

HCID 59266587Methyl 2-chloro-5-ethylthiazole-4-carboxylate

Reagents, catalysts & solvents 3

HCID 62652Cuprous chlorideCatalystHCID 962WaterSolvent2×HCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
0 °C

Procedure

The following diazotization step was adapted from Barton, A.; Breukelman, S. P.; Kaye, P. T.; Meakins, G. D.; Morgan, D. J. J. C. S. Perkin Trans I 1982, 159-164: A solution of NaNO2 (166 mg, 2.4 mmol) in water (0.6 mL) was added slowly to a stirred, cold (0° C.) solution of methyl 2-amino-5-ethyl-1,3-thiazole-4-carboxylate (186 mg, 1.0 mmol), CuSO4·5H2O (330 mg, 1.32 mmol), NaCl (260 mg, 4.45 mmol) and H2SO4 (5.5 mL) in water (7.5 mL). The mixture was stirred at 0° C. for 45 min and allowed to warm up to room temperature where it stirred further for 1 h before CuCl (118 mg) was added. This mixture was stirred further at room temperature for 16 h before it was diluted with brine and extracted with ether twice. The organic layers were combined, dried over MgSO4 and concentrated to give methyl 2-chloro-5-ethylthiazole-4-carboxylate (i.e. Cap-172, step a) (175 mg, 85%) as an orange oil (80% pure) which was used directly in the next reaction. Rt=1.99 min (Cond.-MD1); LC/MS: Anal. Calcd. for [M+H]+ C7H9ClNO2S: 206.01; found: 206.05.

Workup

  1. temperatureto warm up to room temperature where it
  2. additionwas added
  3. stirringThis mixture was stirred further at room temperature for 16 h before it
  4. extractionextracted with ether twice
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-719256c2f3eb45728e11e8f27d06df98
Source dataset
uspto-grants-2014_08
Patent number
US08796466B2

Reaction notes

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