Isoamyl Nitrite → Ethyl 5-chloro-1,3-thiazole-4-carboxylate

HRID 1919565Notes

Reaction equation

HRID 1919565 reaction equation
N[C:2]1[S:3][CH:4]=[C:5]([C:7]([O:9][CH2:10][CH3:11])=[O:8])[N:6]=1.C1C(=O)N([Cl:19])C(=O)C1.N(OCCC(C)C)=O>C(#N)C>[Cl:19][C:4]1[S:3][CH:2]=[N:6][C:5]=1[C:7]([O:9][CH2:10][CH3:11])=[O:8]

Participants

5

Reactant 3

HCID 8053Isoamyl NitriteHCID 31398ChlorosuccinimideHCID 73216Ethyl 2-aminothiazole-4-carboxylate

Product 1

HCID 58758599Ethyl 5-chloro-1,3-thiazole-4-carboxylateYield 84.8%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

21 g (123 mmol) ethyl 2-aminothiazol-4-carboxylate (Example 30, step 1) was added to 150 ml acetonitrile, and 18.4 g (137 mmol) NCS was added portionwise, to carry out reaction at room temperature overnight; and then, 19 ml (137 mmol) isoamyl nitrite was added rapidly dropwise, followed by continuing the reaction for 2 hr after complete of addition. The resultant reaction mixture was concentrated, then ethyl acetate and water were added, and filtered to remove insoluble solids. The organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated to obtain 20 g ethyl 5-chlorothiazol-4-carboxylate 1H NMR (CDCl3) 1.42-1.45 (3H, t, J=7.0 Hz); 4.43-4.46 (2H, m, J=7.0 Hz); 8.68 (1H, s); MS (EI) 191.0 (M+).

Workup

  1. additionwas added portionwise
  2. customreaction at room temperature overnight
  3. customthe reaction for 2 hr after
  4. additioncomplete of addition
  5. customThe resultant reaction mixture
  6. concentrationwas concentrated
  7. additionethyl acetate and water were added
  8. filtrationfiltered
  9. customto remove insoluble solids
  10. dry with materialThe organic phase was dried over anhydrous sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-d88e2bd8c10a401c885b7f0c5380c39e
Source dataset
uspto-grants-2012_05
Patent number
US08168642B2

Reaction notes

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