Hydrochloric Acid → Methyl 4-(5-ethoxy-2-fluoro-phenyl)-5,6-dimethyl-pyridine-2-carboxylate

HRID 2207619Notes

Reaction equation

HRID 2207619 reaction equation
Cl.[O:2]1CCOC[CH2:3]1.[CH2:8]([O:10][C:11]1[CH:12]=[CH:13][C:14]([F:27])=[C:15]([C:17]2[C:22]([CH3:23])=[C:21]([CH3:24])[N:20]=[C:19]([C:25]#N)[CH:18]=2)[CH:16]=1)[CH3:9].C[OH:29]>>[CH2:8]([O:10][C:11]1[CH:12]=[CH:13][C:14]([F:27])=[C:15]([C:17]2[C:22]([CH3:23])=[C:21]([CH3:24])[N:20]=[C:19]([C:25]([O:2][CH3:3])=[O:29])[CH:18]=2)[CH:16]=1)[CH3:9]

Participants

5

Reactant 4

HCID 313Hydrochloric AcidHCID 887MethanolHCID 312751,4-DioxaneHCID 896495904-(5-Ethoxy-2-fluoro-phenyl)-5,6-dimethyl-pyridine-2-carbonitrile

Product 1

HCID 89649357Methyl 4-(5-ethoxy-2-fluoro-phenyl)-5,6-dimethyl-pyridine-2-carboxylate

Procedure

4M HCl in 1,4-dioxan (20 mL, 80 mmol) was added to a suspension of 4-(5-ethoxy-2-fluoro-phenyl)-5,6-dimethyl-pyridine-2-carbonitrile (which may be prepared as described in Description 51) (1.87 g, 6.92 mmol) in methanol (20 mL) at ambient temperature. The stirred, yellow solution was refluxed under N2 for 9 h. The reaction was concentrated to one third the volume then poured into sat. aq. NaHCO3 (100 ml). The mixture was extracted with EtOAc (3×50 ml). The combined organic extracts were dried (Na2SO4) and evaporated to a colourless oil which solidified. This was purified by SiO2 column chromatography: the oil was dissolved in DCM (15 ml) and the solution was applied to a 100 g cartridge which was then eluted on a Biotage SP4 system with a gradient of EtOAc/iso-hexane (0-80%) to afford methyl 4-(5-ethoxy-2-fluoro-phenyl)-5,6-dimethyl-pyridine-2-carboxylate (D52);

Workup

  1. temperatureThe stirred, yellow solution was refluxed under N2 for 9 h
  2. concentrationThe reaction was concentrated to one third the volume
  3. additionthen poured into sat. aq. NaHCO3 (100 ml)
  4. extractionThe mixture was extracted with EtOAc (3×50 ml)
  5. dry with materialThe combined organic extracts were dried (Na2SO4)
  6. customevaporated to a colourless oil which
  7. customThis was purified by SiO2 column chromatography
  8. dissolutionthe oil was dissolved in DCM (15 ml)
  9. washwas then eluted on a Biotage SP4 system with a gradient of EtOAc/iso-hexane (0-80%)

Sources & evidence

ORD record
ord-8aabdd4bc27842679408c555d364774c
Source dataset
uspto-grants-2016_06
Patent number
US09376436B2

Reaction notes

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