Hydrochloric Acid → HCID 69672674, compound

HRID 1426314Notes

Reaction equation

HRID 1426314 reaction equation
[F:1][C:2]([F:7])([F:6])[C:3](=[NH:5])[NH2:4].O/[C:9](/[CH:18]([CH3:20])[CH3:19])=[CH:10]\[C:11](=O)[C:12]([O:14][CH2:15][CH3:16])=[O:13].Cl>C(O)C>[CH:18]([C:9]1[N:4]=[C:3]([C:2]([F:7])([F:6])[F:1])[N:5]=[C:11]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH:10]=1)([CH3:20])[CH3:19]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 2776882TrifluoroacetamidineHCID 178473096HCID 178473096, compound

Product 1

HCID 69672674HCID 69672674, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

To a solution of 2,2,2-trifluoroethanimidamide (7.08 g, 53.7 mmol, Matrix) in ethanol (85 mL, 1400 mmol) was added ethyl (3Z)-4-hydroxy-5-methyl-2-oxohex-3-enoate (10.00 g, 53.70 mmol, Alfa Aesar). The mixture was then cooled in an ice bath, and a solution of hydrogen chloride in ethanol (84 mL, prepared by bubbling HCl gas through the ethanol for 10 minutes) was added. The reaction was allowed to warm to room temperature and stir overnight. The mixture was added dropwise to a saturated solution of sodium bicarbonate. After complete neutralization was achieved, 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 crude product was purified by flash chromatography on silica gel, eluting with a gradient from 0-25% EtOAc/Hexanes (9.14 g, 65%). 1H NMR (300 MHz, CDCl3) δ 8.02 (s, 1H), 4.52 (q, J=7.1 Hz, 2H), 3.22 (hept, J=6.9 Hz, 1H), 1.45 (t, J=7.1 Hz, 3H), 1.38 (d, J=6.9 Hz, 6H); LCMS (M+H)+: 263.1

Workup

  1. temperatureThe mixture was then cooled in an ice bath
  2. customby bubbling HCl gas through the ethanol for 10 minutes)
  3. additionwas added
  4. additionThe mixture was added dropwise to a saturated solution of sodium bicarbonate
  5. customethanol was removed in vacuo
  6. extractionThe product was extracted with three portions of DCM
  7. dry with materialThe combined extracts were dried over sodium sulfate
  8. filtrationfiltered
  9. customevaporated
  10. customThe crude product was purified by flash chromatography on silica gel
  11. washeluting with a gradient from 0-25% EtOAc/Hexanes (9.14 g, 65%)

Sources & evidence

ORD record
ord-2f3c6adff7494b10a51bd36c4dc8a1a2
Source dataset
uspto-grants-2015_01
Patent number
US08933085B2

Reaction notes

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