Thieno(3,2-c)pyridine → 1-(Thieno[3,2-c]pyridin-2-yl)ethanone

HRID 1775402Notes

Reaction equation

HRID 1775402 reaction equation
[S:1]1[C:9]2[CH:8]=[CH:7][N:6]=[CH:5][C:4]=2[CH:3]=[CH:2]1.C([Li])CCC.CN(OC)[C:17](=[O:19])[CH3:18]>O1CCCC1>[S:1]1[C:9]2[CH:8]=[CH:7][N:6]=[CH:5][C:4]=2[CH:3]=[C:2]1[C:17](=[O:19])[CH3:18]

Participants

5

Reactant 3

HCID 67500Thieno(3,2-c)pyridineHCID 537505N-Methoxy-N-methylacetamideHCID 178418339Butyllithium

Product 1

HCID 584330461-(Thieno[3,2-c]pyridin-2-yl)ethanone

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-45 °C

Procedure

A solution of thieno[3,2-c]pyridine (5.0 g) in 75 mL THF (tetrahydrofuran) was cooled to −45° C. in a CH3CN/dry ice bath. n-Butyllithium (1.6M in hexanes) (35.0 ml) was added dropwise maintaining the internal temperature at or below −40° C. The addition took about 45 minutes. The reaction was stirred for 1 hour at −45° C. N-methyl-N-methoxyacetamide in 5 mL THF was added and as a result the reaction warmed to −30° C. The reaction was stirred at −45° C. for 1.5 hours. The reaction was quenched with saturated NH4Cl. The aqueous layer had a pH of about 8. The aqueous layer was extracted three times into EtOAc. The combined organic extracts were washed with brine and dried over MgSO4. The material was filtered, concentrated on a rotary evaporator and subjected to column chromatography (Biotage Horizon system, 120 g Analogix column, equilibrate with hexanes, elute with 50% EtOAc/hexanes). The most pure fractions were concentrated on a rotary evaporator and then triturated with Et2O to remove some color and collect a pale orange solid by filtration (2.667 g).

Workup

  1. temperaturemaintaining the internal temperature at or below −40° C
  2. additionThe addition
  3. customas a result the reaction
  4. temperaturewarmed to −30° C
  5. stirringThe reaction was stirred at −45° C. for 1.5 hours
  6. customThe reaction was quenched with saturated NH4Cl
  7. extractionThe aqueous layer was extracted three times into EtOAc
  8. washThe combined organic extracts were washed with brine
  9. dry with materialdried over MgSO4
  10. filtrationThe material was filtered
  11. concentrationconcentrated on a rotary evaporator
  12. washsubjected to column chromatography (Biotage Horizon system, 120 g Analogix column, equilibrate with hexanes, elute with 50% EtOAc/hexanes)
  13. concentrationThe most pure fractions were concentrated on a rotary evaporator
  14. customtriturated with Et2O
  15. customto remove some color
  16. customcollect a pale orange solid
  17. filtrationby filtration (2.667 g)

Sources & evidence

ORD record
ord-e83f9c4ad6ee476d9c4a6f51c31c62f3
Source dataset
uspto-grants-2016_02
Patent number
US09260450B2

Reaction notes

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