Methyl 3-mercaptopropionate → 4-(2-Methoxycarbonyl-ethylsulfanyl)-pyridine-3-carboxylic acid ethyl ester

HRID 925267Notes

Reaction equation

HRID 925267 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[CH:7]=[N:8][CH:9]=[CH:10][C:11]=1Cl)=[O:5])[CH3:2].CC(C)([O-])C.[K+].[SH:19][CH2:20][CH2:21][C:22]([O:24][CH3:25])=[O:23]>O1CCCC1>[CH2:1]([O:3][C:4]([C:6]1[CH:7]=[N:8][CH:9]=[CH:10][C:11]=1[S:19][CH2:20][CH2:21][C:22]([O:24][CH3:25])=[O:23])=[O:5])[CH3:2]

Participants

5

Reactant 3

HCID 18050Methyl 3-mercaptopropionateHCID 14116704Ethyl 4-chloropyridine-3-carboxylateHCID 23665647Potassium tert-butoxide

Product 1

HCID 867201644-(2-Methoxycarbonyl-ethylsulfanyl)-pyridine-3-carboxylic acid ethyl esterYield 48.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 4-chloro-pyridine-3-carboxylic acid ethyl ester (4.30 g, 23.2 mmol) in dry tetrahydrofuran (45 ml) is added potassium tert-butoxide (3.12 g, 27.9 mmol) portion wise at 0° C., followed by the addition of methyl 3-mercaptopropanoate (3.35 g, 27.9 mmol). The reaction mixture is stirred at RT for 2 h. After completion of the reaction, the solvent is distilled off and the residue is diluted with water (30 ml). The aqueous layer is extracted with EtOAc (3×40 ml). The combined organic layers are washed with water (40 ml), brine (40 ml), dried over anhydrous sodium sulfate and evaporated to get the crude product, which is purified by column chromatography (silica gel, 30% EtOAc/hexane) to get 4-(2-methoxycarbonyl-ethylsulfanyl)-pyridine-3-carboxylic acid ethyl ester (3.0 g, 11.2 mmol, 48%).

Workup

  1. customAfter completion of the reaction
  2. distillationthe solvent is distilled off
  3. additionthe residue is diluted with water (30 ml)
  4. extractionThe aqueous layer is extracted with EtOAc (3×40 ml)
  5. washThe combined organic layers are washed with water (40 ml), brine (40 ml)
  6. dry with materialdried over anhydrous sodium sulfate
  7. customevaporated
  8. customto get the crude product, which
  9. customis purified by column chromatography (silica gel, 30% EtOAc/hexane)

Sources & evidence

ORD record
ord-ea005294d66549e0a9b3a95eed2a98eb
Source dataset
uspto-grants-2016_03
Patent number
US09284286B2

Reaction notes

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