Hydrochloric Acid → HCID 69672849, compound

HRID 1426318Notes

Reaction equation

HRID 1426318 reaction equation
[F:1][C:2]([F:7])([F:6])[C:3](=[NH:5])[NH2:4].[CH:8]1(/[C:12](/O)=[CH:13]/[C:14](=O)[C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH2:11][CH2:10][CH2:9]1.Cl>C(O)C>[CH:8]1([C:12]2[N:4]=[C:3]([C:2]([F:7])([F:6])[F:1])[N:5]=[C:14]([C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH:13]=2)[CH2:9][CH2:10][CH2:11]1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 2776882TrifluoroacetamidineHCID 178473077HCID 178473077, compound

Product 1

HCID 69672849HCID 69672849, compoundYield 48.3%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent3×

Procedure

To a solution of 2,2,2-trifluoroethanimidamide (1.80 g, 13.6 mmol, Matrix) in ethanol (22 mL, 370 mmol) was added a solution of ethyl (3Z)-4-cyclobutyl-4-hydroxy-2-oxobut-3-enoate (2.7 g, 14 mmol, from Step A) in a small volume of ethanol. The solution was cooled in an ice bath and a solution of hydrogen chloride in ethanol (21 mL, 360 mmol, prepared by bubbling HCl gas through the ethanol for 10 minutes) was added. The reaction was allowed to warm to room temperature and stirred overnight. The mixture was added slowly to a saturated solution of sodium bicarbonate. Additional solid potassium carbonate was added. After neutralization was complete, ethanol was removed in vacuo. The product was extracted with three portions of DCM. The combined extracts were dried over sodium sulfate, filtered and evaporated. The product was purified by flash chromatography on silica gel, eluting with a gradient from 0-25% EtOAc/hexanes to afford a yellow oil (1.8 g, 48%). 1H NMR (400 MHz, CDCl3) δ 7.98 (s, 1H), 4.51 (q, J=7.1 Hz, 2H), 3.81 (p, J=8.6 Hz, 1H), 2.48-2.33 (m, 4H), 2.21-2.08 (m, 1H), 2.03-1.93 (m, 1H), 1.45 (t, J=7.1 Hz, 3H); LCMS (M+H)+: 275.1

Workup

  1. temperatureThe solution was cooled in an ice bath
  2. customby bubbling HCl gas through the ethanol for 10 minutes)
  3. additionwas added
  4. additionThe mixture was added slowly to a saturated solution of sodium bicarbonate
  5. additionAdditional solid potassium carbonate was added
  6. customethanol was removed in vacuo
  7. extractionThe product was extracted with three portions of DCM
  8. dry with materialThe combined extracts were dried over sodium sulfate
  9. filtrationfiltered
  10. customevaporated
  11. customThe product was purified by flash chromatography on silica gel
  12. washeluting with a gradient from 0-25% EtOAc/hexanes

Sources & evidence

ORD record
ord-157e919991e546e28bb795b468aee624
Source dataset
uspto-grants-2015_01
Patent number
US08933085B2

Reaction notes

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