Hydrochloric Acid → Ethyl 2-(4-chloro-5-fluoro-3-methyl-2-pyridinyl)cyclopropaneacetate

HRID 1600999Notes

Reaction equation

HRID 1600999 reaction equation
[Cl:1][C:2]1[C:7]([F:8])=[CH:6][N:5]=[C:4]([CH:9]2[CH2:11][CH:10]2[CH2:12][C:13]#N)[C:3]=1[CH3:15].Cl.O.C([O-])(O)=[O:19].[Na+].[CH2:23]([OH:25])[CH3:24]>>[Cl:1][C:2]1[C:7]([F:8])=[CH:6][N:5]=[C:4]([CH:9]2[CH2:11][CH:10]2[CH2:12][C:13]([O:25][CH2:23][CH3:24])=[O:19])[C:3]=1[CH3:15]

Participants

6

Reactant 5

HCID 313Hydrochloric AcidHCID 702EthanolHCID 962Water2×HCID 516892Sodium BicarbonateHCID 224747832-(4-Chloro-5-fluoro-3-methyl-2-pyridinyl)cyclopropaneacetonitrile

Product 1

HCID 17876874Ethyl 2-(4-chloro-5-fluoro-3-methyl-2-pyridinyl)cyclopropaneacetate

Procedure

A sample of 2-(4-chloro-5-fluoro-3-methyl-2-pyridinyl)cyclopropaneacetonitrile (3.26 g, 14.51 mmol) was dissolved in 10 mL of ethanol, and gaseous HCl was introduced until 4 g had been dissolved. The solution was heated to reflux, and 0.36 mL of water was added, then the mixture was stirred for 1 hour. The reaction was cooled, then poured into water, and the mixture was adjusted to pH7 with NaHCO3. The mixture was then extracted with methylene chloride, which was washed with water, dried over MgSO4 and concentrated. The residue was triturated with 1:4 ethyl acetate:hexane, and filtered. The filtrate was concentrated and the residue was purified by flash chromatography with 1:4 ethyl acetate:hexane to give 2.262 g of ethyl 2-(4-chloro-5-fluoro-3-methyl-2-pyridinyl)cyclopropaneacetate after removal of the solvent. MS 272, 274 (M+H)+ ; 1H NMR (CDCl3)∂: 0.12 (m, 1H), 0.38 (m, 1H), 0.53 (m, 1H), 0.76 (m, 1H), 1.20 (t, 3H, J=7 Hz), 1.67 (m, 1H), 2.40 (s, 3H), 3.23 (d, 1H, J=9 Hz), 4.16 (q, 2H, J=7 Hz), 8.36 (s, 1H).

Workup

  1. dissolutionhad been dissolved
  2. temperatureThe solution was heated
  3. temperatureto reflux
  4. temperatureThe reaction was cooled
  5. extractionThe mixture was then extracted with methylene chloride, which
  6. washwas washed with water
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated
  9. customThe residue was triturated with 1:4 ethyl acetate
  10. filtrationhexane, and filtered
  11. concentrationThe filtrate was concentrated
  12. customthe residue was purified by flash chromatography with 1:4 ethyl acetate

Sources & evidence

ORD record
ord-694bc438cb0345a4b9e2e35509be3330
Source dataset
uspto-grants-1999_11
Patent number
US05977133

Reaction notes

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