Hydrochloric Acid → HCID 57756680, compound

HRID 227659Notes

Reaction equation

HRID 227659 reaction equation
N(OC(C)(C)C)=O.N[C:9]1[S:10][C:11]([C:26]([O:28][CH2:29][CH3:30])=[O:27])=[C:12]([O:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[C:22]([F:25])([F:24])[F:23])[N:13]=1.[ClH:31]>C(#N)C.[Cu]Cl>[Cl:31][C:9]1[S:10][C:11]([C:26]([O:28][CH2:29][CH3:30])=[O:27])=[C:12]([O:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[C:22]([F:25])([F:24])[F:23])[N:13]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 10906Tert-Butyl nitriteHCID 57756682HCID 57756682, compound

Product 1

HCID 57756680HCID 57756680, compoundYield 51%

Reagents, catalysts & solvents 2

HCID 62652Cuprous chlorideCatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
65 °C

Procedure

Copper(I) chloride (0.342 g, 3.45 mmol) and t-butyl nitrite (0.52 mL, 4.37 mmol) were stirred in 20 mL of acetonitrile. Ethyl 2-amino-4-({[2-(trifluoromethyl)-phenyl]methyl}oxy)-1,3-thiazole-5-carboxylate (1.00 g, 2.88 mmol) was added, and the reaction was stirred for 1.5 hours. The reaction was heated to 65° C. with an oil bath for an hour and cooled to room temperature. The reaction mixture was slowly pipeted onto 40 mL of 6N HCl stirring at 0° C. The ice bath was removed, and the mixture was warmed to room temperature, where it stirred for 30 minutes. The mixture was poured into ethyl acetate and water, and the layers were separated. The organic layer was washed with brine, and the combined aqueous layers were extracted with ethyl acetate. The combined organic layers were dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by flash chromatography to provide 0.537 g (51%) of ethyl 2-chloro-4-({[2-(trifluoromethyl)phenyl]methyl}oxy)-1,3-thiazole-5-carboxylate. 1H NMR (400 MHz, DMSO-d6) δ 7.88-7.73 (m, 3H), 7.60 (m, 1H), 5.63 (s, 2H), 4.24 (q, J=7.1 Hz, 2H), 1.25 (t, J=7.1 Hz, 3H).

Workup

  1. temperaturecooled to room temperature
  2. customThe ice bath was removed
  3. temperaturethe mixture was warmed to room temperature
  4. stirringwhere it stirred for 30 minutes
  5. additionThe mixture was poured into ethyl acetate and water
  6. customthe layers were separated
  7. washThe organic layer was washed with brine
  8. extractionthe combined aqueous layers were extracted with ethyl acetate
  9. dry with materialThe combined organic layers were dried over MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customThe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-fc535f8986de4ce3bdf3b8866ca0bb6f
Source dataset
uspto-grants-2009_07
Patent number
US07560568B2

Reaction notes

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