Sodium Hydroxide → (6-Methylpyridin-3-yl)acetic acid

HRID 2369258Notes

Reaction equation

HRID 2369258 reaction equation
[CH3:1][C:2]1[N:7]=[CH:6][C:5]([CH2:8][C:9](N2CCOCC2)=S)=[CH:4][CH:3]=1.[OH-:17].[Na+].[OH2:19].CCO>>[CH3:1][C:2]1[N:7]=[CH:6][C:5]([CH2:8][C:9]([OH:19])=[O:17])=[CH:4][CH:3]=1

Participants

4

Reactant 3

HCID 14798Sodium HydroxideHCID 2727779HCID 2727779, compoundHCID 19096565Water ethanol

Product 1

HCID 22507698(6-Methylpyridin-3-yl)acetic acidYield 46%

Procedure

Crude 2-(6-methyl-pyridin-3-yl)-1-morpholin-4-yl-ethanethione (39.5 mmol, 9.685 g) was suspended in 2:1 H2O/EtOH (40 mL). NaOH (3.3 eq., 118.5 mmol, 4.8 g) was added and the reaction heated to reflux for 16 hours. The volatiles were then removed from the cooled reaction medium, and the pH adjusted to precisely pH 7.0 with 3.0 M HCl. The solvent was removed and the residue slurried in boiling methanol, filtered whilst hot, and the filtrate evaporated to dryness. This crude product contains residual free morpholine, which was removed by flash column chromatography, eluting with 9:1 EtOAc/MeOH. The fractions were analysed by TLC eluting with 1:1 EtOAc/MeOH (Rf=0.209). The product was obtained in 46% yield.

Workup

  1. temperaturethe reaction heated
  2. temperatureto reflux for 16 hours
  3. customThe volatiles were then removed from the cooled reaction medium
  4. customThe solvent was removed
  5. filtrationfiltered whilst hot, and the filtrate
  6. customevaporated to dryness
  7. customwas removed by flash column chromatography
  8. washeluting with 9:1 EtOAc/MeOH
  9. washeluting with 1:1 EtOAc/MeOH (Rf=0.209)
  10. customThe product was obtained in 46% yield

Sources & evidence

ORD record
ord-e5424a8078b04104aa1fc0eb13db5c40
Source dataset
uspto-grants-2014_04
Patent number
US08703952B2

Reaction notes

Loading…