Methyl 3-mercaptopropionate → Methyl 3-[(5,6-dimethoxypyridin-3-yl)sulfanyl]propanoate

HRID 709022Notes

Reaction equation

HRID 709022 reaction equation
Br[C:2]1[CH:3]=[C:4]([O:10][CH3:11])[C:5]([O:8][CH3:9])=[N:6][CH:7]=1.[SH:12][CH2:13][CH2:14][C:15]([O:17][CH3:18])=[O:16].C(N(C(C)C)C(C)C)C>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>[CH3:11][O:10][C:4]1[CH:3]=[C:2]([S:12][CH2:13][CH2:14][C:15]([O:17][CH3:18])=[O:16])[CH:7]=[N:6][C:5]=1[O:8][CH3:9]

Participants

7

Reactant 3

HCID 18050Methyl 3-mercaptopropionateHCID 81531DiisopropylethylamineHCID 125630845-Bromo-2,3-dimethoxypyridine

Product 1

HCID 71185962Methyl 3-[(5,6-dimethoxypyridin-3-yl)sulfanyl]propanoateYield 105.1%

Reagents, catalysts & solvents 3

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Procedure

To a solution of 5-bromo-2,3-dimethoxypyridine (2 g, 9.17 mmol) in dioxane (30 ml) was added methyl 3-sulfanylpropanoate (1.21 g, 10.1 mmol), N-ethyl-N-isopropylpropan-2-amine (3.03 ml, 18.3 mmol), Pd2(dba)3 (0.34 g, 0.37 mmol) and Xantphos (0.43 g, 0.73 mmol) at room temperature under an atmosphere of nitrogen. The reaction was degassed by evacuating and flushing with nitrogen and heated at reflux for 18 hours and then allowed to cool and filtered, washing with ethyl acetate. The filtrate was concentrated under reduced pressure to give an orange oil. Purification by column chromatography (SiO2; 0-20% ethyl acetate in petrol), gave methyl 3-[(5,6-dimethoxypyridin-3-yl)sulfanyl]propanoate as a yellow oil (2.48 g, quantitative yield).

Workup

  1. customThe reaction was degassed
  2. customby evacuating
  3. customflushing with nitrogen
  4. temperatureheated
  5. temperatureat reflux for 18 hours
  6. temperatureto cool
  7. filtrationfiltered
  8. washwashing with ethyl acetate
  9. concentrationThe filtrate was concentrated under reduced pressure
  10. customto give an orange oil
  11. customPurification by column chromatography (SiO2; 0-20% ethyl acetate in petrol)

Sources & evidence

ORD record
ord-3605c11a11c6418797d31b2d9e413b93
Source dataset
uspto-grants-2015_11
Patent number
US09180122B2

Reaction notes

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