Hydrochloric Acid → Ethyl 3-methylthieno[3,2-b]pyridine-2-carboxylate

HRID 2091315Notes

Reaction equation

HRID 2091315 reaction equation
Cl[C:2]1[C:3]([C:8]#N)=[N:4][CH:5]=[CH:6][CH:7]=1.C[Mg]Br.Cl.[SH:14][CH2:15][C:16]([O:18][CH2:19][CH3:20])=[O:17].[C:21](=O)([O-])[O-].[K+].[K+]>O1CCCC1.C(OCC)C.O>[CH3:21][C:8]1[C:3]2=[N:4][CH:5]=[CH:6][CH:7]=[C:2]2[S:14][C:15]=1[C:16]([O:18][CH2:19][CH3:20])=[O:17]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 12185Ethyl ThioglycolateHCID 8182583-Chloropyridine-2-carbonitrileHCID 178418573HCID 178418573, compound

Product 1

HCID 66777092Ethyl 3-methylthieno[3,2-b]pyridine-2-carboxylateYield 79%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution (100 mL) of 3-chloropyridine-2-carbonitrile (10.0 g) in tetrahydrofuran was added a 3.0M solution (48.0 mL) of methylmagnesium bromide in diethyl ether, and the mixture was stirred at room temperature for 3 hr. To the reaction mixture was added 2N hydrochloric acid (300 mL), tetrahydrofuran was evaporated in an evaporator, and the residue was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (30-70% ethyl acetate/hexane) to give a pale-yellow oil. To a mixture of the obtained oil, ethyl mercaptoacetate (4.23 mL) and N,N-dimethylformmide (60 mL) was added and potassium carbonate (16.0 g), and the mixture was stirred overnight at 50° C. Water was added to quench the reaction, and the precipitated solid was collected by filtration to give the title object compound (6.75 g, 79%) as a white solid.

Workup

  1. customwas evaporated in an evaporator
  2. extractionthe residue was extracted with ethyl acetate
  3. washThe extract was washed with saturated brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (30-70% ethyl acetate/hexane)
  7. customto give a pale-yellow oil
  8. additionwas added
  9. customto quench
  10. customthe reaction
  11. filtrationthe precipitated solid was collected by filtration

Sources & evidence

ORD record
ord-b0ea4cf7f6854c0c92eae3d8bc9c8f30
Source dataset
uspto-grants-2013_05
Patent number
US08436043B2

Reaction notes

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