Hydrochloric Acid → 3-Hydroxy-2-(6-trifluoromethylpyridin-3-yl)-acrylic acid ethyl ester

HRID 889299Notes

Reaction equation

HRID 889299 reaction equation
[CH2:1]([O:3][C:4](=[O:16])[CH2:5][C:6]1[CH:7]=[N:8][C:9]([C:12]([F:15])([F:14])[F:13])=[CH:10][CH:11]=1)[CH3:2].[H-].[Na+].C1OCCOCCOCCOCCOCC[O:21][CH2:20]1.C(OC=O)C.Cl>C(OCC)(=O)C.C1(C)C=CC=CC=1>[CH2:1]([O:3][C:4](=[O:16])[C:5]([C:6]1[CH:7]=[N:8][C:9]([C:12]([F:13])([F:14])[F:15])=[CH:10][CH:11]=1)=[CH:20][OH:21])[CH3:2]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 8025Ethyl formateHCID 24758Sodium hydrideHCID 2855718-Crown-6HCID 59186932(6-Trifluoromethylpyridin-3-yl)-acetic acid ethyl ester

Product 1

HCID 687048893-Hydroxy-2-(6-trifluoromethylpyridin-3-yl)-acrylic acid ethyl ester

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

3.46 g (14.8 mmol) of the compound from Example 40A are initially introduced into 50 ml anhydrous toluene under argon, 712 mg (17.8 mmol) sodium hydride suspension (60% strength in paraffin oil) are added in portions and the mixture is stirred at RT for 1 h and then at 80° C. for 20 min. After cooling, 392 mg (1.48 mmol) 18-crown-6 and then, while cooling with ice, 2.20 g (29.7 mol) formic acid ethyl ester are added dropwise. The mixture is stirred first at 0° C. for 1 h and then at RT for 1 h. A mixture of 100 ml ethyl acetate and 150 ml 0.1 M hydrochloric acid is added, the phases are separated, the aqueous phase is extracted several times with ethyl acetate and the combined organic phases are dried over sodium sulfate, filtered and concentrated. The residue is purified by means of flash chromatography on silica gel (mobile phase: cyclohexane/ethyl acetate gradient).

Workup

  1. waitat 80° C. for 20 min
  2. temperatureAfter cooling
  3. additionare added dropwise
  4. stirringThe mixture is stirred first at 0° C. for 1 h
  5. waitat RT for 1 h
  6. additionis added
  7. customthe phases are separated
  8. extractionthe aqueous phase is extracted several times with ethyl acetate
  9. dry with materialthe combined organic phases are dried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customThe residue is purified by means of flash chromatography on silica gel (mobile phase: cyclohexane/ethyl acetate gradient)

Sources & evidence

ORD record
ord-ff1e219c097245258bd55d56a02c6eee
Source dataset
uspto-grants-2012_08
Patent number
US08252817B2

Reaction notes

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