Methyl 3-mercaptopropionate → Methyl 3-{[5,6-bis(methoxymethoxy)pyridin-3-yl]sulfanyl}propanoate

HRID 709056Notes

Reaction equation

HRID 709056 reaction equation
Br[C:2]1[CH:3]=[C:4]([O:12][CH2:13][O:14][CH3:15])[C:5]([O:8][CH2:9][O:10][CH3:11])=[N:6][CH:7]=1.CCN(C(C)C)C(C)C.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.[SH:67][CH2:68][CH2:69][C:70]([O:72][CH3:73])=[O:71]>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]>[CH3:15][O:14][CH2:13][O:12][C:4]1[CH:3]=[C:2]([S:67][CH2:68][CH2:69][C:70]([O:72][CH3:73])=[O:71])[CH:7]=[N:6][C:5]=1[O:8][CH2:9][O:10][CH3:11]

Participants

7

Reactant 4

HCID 18050Methyl 3-mercaptopropionateHCID 81531DiisopropylethylamineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 867315425-Bromo-2,3-bis(methoxymethoxy)pyridine2×

Product 1

HCID 86731543Methyl 3-{[5,6-bis(methoxymethoxy)pyridin-3-yl]sulfanyl}propanoateYield 72.3%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent2×

Procedure

A solution of 5-bromo-2,3-bis(methoxymethoxy)pyridine (Intermediate 41; 2 g, 7.19 mmol) in dioxane 40.0 ml) was degassed and to this was added DIPEA (2.51 ml, 14.38 mmol), Xantphos (0.333 g, 0.575 mmol) and Pd2(dba)3 (0.263 g, 0.288 mmol). Methyl 3-mercaptopropanoate (0.951 g, 7.91 mmol) was then added as a solution in dioxane (4 mL) and the reaction was heated under reflux for 1 hour before being cooled to room temperature and filtered through a pad of celite, washing with ethyl acetate. The combined organics were washed with water and then brine, dried (MgSO4) and then concentrated in vacuo. The crude product was purified by column chromatography (SiO2; 0-50% ethyl acetate/petrol) to yield methyl 3-{[5,6-bis(methoxymethoxy)pyridin-3-yl]sulfanyl}propanoate (1.65 g, 72%).

Workup

  1. temperaturethe reaction was heated
  2. temperatureunder reflux for 1 hour
  3. filtrationfiltered through a pad of celite
  4. washwashing with ethyl acetate
  5. washThe combined organics were washed with water
  6. dry with materialbrine, dried (MgSO4)
  7. concentrationconcentrated in vacuo
  8. customThe crude product was purified by column chromatography (SiO2; 0-50% ethyl acetate/petrol)

Sources & evidence

ORD record
ord-b2ccd55ae19f4d8783270f4ff2d76cf5
Source dataset
uspto-grants-2015_11
Patent number
US09180122B2

Reaction notes

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