Ammonia → HCID 57756682, compound

HRID 227658Notes

Reaction equation

HRID 227658 reaction equation
C([NH:4][C:5]1[S:6][C:7]([C:22]([O:24][CH2:25][CH3:26])=[O:23])=[C:8]([O:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[C:18]([F:21])([F:20])[F:19])[N:9]=1)(=O)C.N.CO>>[NH2:4][C:5]1[S:6][C:7]([C:22]([O:24][CH2:25][CH3:26])=[O:23])=[C:8]([O:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[C:18]([F:21])([F:19])[F:20])[N:9]=1

Participants

4

Reactant 3

HCID 222AmmoniaHCID 887MethanolHCID 57756685HCID 57756685, compound

Product 1

HCID 57756682HCID 57756682, compoundYield 87%

Conditions

Temperature
80 °C

Procedure

Ethyl 2-(acetylamino)-4-({[2-(trifluoromethyl)-phenyl]methyl}oxy)-1,3-thiazole-5-carboxylate (6.23 g, 16.0 mmol) was placed in a pressure vessel with a stir bar. 2N Ammonia in methanol (120 mL, 240 mmol) was added via syringe and the vessel was sealed. The solution was heated to 80° C. using an oil bath for 16 hours. The reaction was cooled and concentrated. The residue was dissolved in ethyl acetate and washed with half-saturated NaHCO3 and brine. The combined aqueous layers were extracted with ethyl acetate. The combined organic layers were dried over MgSO4, filtered, and concentrated in vacuo. The solid was dissolved in approximately 50 mL of dichloromethane, and 150 mL of hexanes was added. Air was blown over the solution and hexanes added periodically to precipitate the product. The solid was filtered, washed with hexanes, and air-dried to afford 4.80 g (87%) of ethyl 2-amino-4-({[2-(trifluoromethyl)-phenyl]methyl}oxy)-1,3-thiazole-5-carboxylate as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 8.14 (s, 2H), 7.90 (d, J=7.7 Hz, 1H), 7.81-7.72 (m, 2H), 7.57 (m, 1H), 5.52 (s, 2H), 4.11 (q, J=7.1 Hz, 2H), 1.21 (t, J=7.1 Hz, 3H).

Workup

  1. customthe vessel was sealed
  2. customfor 16 hours
  3. temperatureThe reaction was cooled
  4. concentrationconcentrated
  5. dissolutionThe residue was dissolved in ethyl acetate
  6. washwashed with half-saturated NaHCO3 and brine
  7. extractionThe combined aqueous layers were extracted with ethyl acetate
  8. dry with materialThe combined organic layers were dried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. dissolutionThe solid was dissolved in approximately 50 mL of dichloromethane
  12. addition150 mL of hexanes was added
  13. additionadded periodically
  14. customto precipitate the product
  15. filtrationThe solid was filtered
  16. washwashed with hexanes
  17. customair-dried

Sources & evidence

ORD record
ord-7b4c8c0796464c808bac8592f6341c5d
Source dataset
uspto-grants-2009_07
Patent number
US07560568B2

Reaction notes

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