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Methanol → HCID 14178173, compound

HRID 1789223
Notes
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Reaction equation

HRID 1789223 reaction equation
[CH3:1][O:2][C:3](=[O:14])[CH2:4][CH:5](O)[C:6]1[CH:7]=[CH:8][C:9]([CH3:12])=[N:10][CH:11]=1.C(OC(=O)C)(=O)C.CO.[H][H]>C1(C)C=CC=CC=1.C(O)(=O)C.[Pd]>[CH3:1][O:2][C:3](=[O:14])[CH2:4][CH2:5][C:6]1[CH:7]=[CH:8][C:9]([CH3:12])=[N:10][CH:11]=1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

8

Reactant 4

HCID 887MethanolHCID 7918Acetic AnhydrideHCID 14178172Methyl 3-hydroxy-3-(6-methylpyridin-3-yl)propanoateHCID 178418361HCID 178418361, compound

Product 1

HCID 14178173HCID 14178173, compoundYield 114%

Reagents, catalysts & solvents 3

HCID 23938
Palladium
Catalyst
HCID 176Acetic AcidSolvent
HCID 1140TolueneSolvent

Conditions

Temperature
60 °C

Procedure

80.0 g (0.35 mol) of recrystallized 3-hydroxy-3-(2-methyl-5-pyridyl)-propionic acid methyl ester was dissolved in 100 ml of toluene. 60.0 g (0.588 mol) of acetic anhydride and 0.1 g (0.0009 mol) of 4-dimethyl-aminopyridine were added, and the solution was stirred for 1 hour at 60° C. Then 20 ml of methanol was added. After 15 minutes, the solution was diluted with 250 ml of acetic acid, 1.5 g of 5 percent palladium on activated carbon was added, and the solution was poured into the autoclave. The hydrogenation was performed under 8 bars of hydrogen at 65° C. for 5.5 hours. At the end of the hydrogenation, the autoclave was cooled, and the solution was filtered and evaporated. The evaporation residue was dissolved in 100 ml of water and 100 ml of methylene chloride and adjusted to pH 7 with 87.9 g of 40 percent sodium hydroxide solution. The phases were separated, the aqueous phase was extracted with methylene chloride, and the combined organic extracts were evaporated. 71.5 g of raw 2-methylpyridine-5-propionic acid methyl ester was obtained. (Content according to GC, 91.5 percent; yield, 92.1 percent in relation to the 3-hydroxy-3-(2-methyl-5-pyridyl)-propionic acid methyl ester used.) The product was distilled to obtain a 97 percent product having with a boiling point of 100°-113° C./1-2 mbar. The yield of distilled product was 88.5 percent, in relation to the 3-hydroxy-3-(2-methyl-5-pyridyl)-propionic acid methyl ester used.

Workup

  1. waitAfter 15 minutes
  2. additionwas added
  3. additionthe solution was poured into the autoclave
  4. temperatureAt the end of the hydrogenation, the autoclave was cooled
  5. filtrationthe solution was filtered
  6. customevaporated
  7. dissolutionThe evaporation residue was dissolved in 100 ml of water
  8. customThe phases were separated
  9. extractionthe aqueous phase was extracted with methylene chloride
  10. customthe combined organic extracts were evaporated

Sources & evidence

ORD record
ord-6fcb5bbb70f740b3b196d7724ee508c4
Source dataset
uspto-grants-1987_08
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US04687856

Reaction notes

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