Nicotinoyl chloride → Ethyl 3-oxo-3-(pyridin-3-yl)-2-(thiophen-3-yl)propanoate

HRID 924650Notes

Reaction equation

HRID 924650 reaction equation
[S:1]1[CH:5]=[CH:4][C:3]([CH2:6][C:7]([O:9][CH2:10][CH3:11])=[O:8])=[CH:2]1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[C:22](Cl)(=[O:29])[C:23]1[CH:28]=[CH:27][CH:26]=[N:25][CH:24]=1>C1COCC1>[O:29]=[C:22]([C:23]1[CH:24]=[N:25][CH:26]=[CH:27][CH:28]=1)[CH:6]([C:3]1[CH:4]=[CH:5][S:1][CH:2]=1)[C:7]([O:9][CH2:10][CH3:11])=[O:8]

Participants

5

Reactant 3

HCID 82604Nicotinoyl chlorideHCID 520865Ethyl 3-thiopheneacetateHCID 2733832Lithium Hexamethyldisilazide

Product 1

HCID 66665073Ethyl 3-oxo-3-(pyridin-3-yl)-2-(thiophen-3-yl)propanoateYield 38%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of ethyl 2-(thiophen-3-yl)acetate (2.3 g, 16.2 mmol) in anhydrous THF (20 mL) was added LiHMDS (19.4 mL, 19.44 mmol) at −78° C. After stirring at that temperature for 0.5 h, a solution of nicotinoyl chloride (2.8 g, 16.2 mmol) in anhydrous THF (10 mL) was added into the reaction mixture and stirred at −78° C. for 4 hours. The mixture was quenched with NH4Cl solution, extracted with EtOAc. The organic layer was concentrated in vacuo and purified by silica gel column chromatography (1.7 g, yield 38%).

Workup

  1. stirringstirred at −78° C. for 4 hours
  2. customThe mixture was quenched with NH4Cl solution
  3. extractionextracted with EtOAc
  4. concentrationThe organic layer was concentrated in vacuo
  5. custompurified by silica gel column chromatography (1.7 g, yield 38%)

Sources & evidence

ORD record
ord-2aa756ba39dc4badb95f81733571bac0
Source dataset
uspto-grants-2016_03
Patent number
US09283213B2

Reaction notes

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