Cyanoacetic acid → 6-(5-Bromothiophen-2-yl)-3,6-dioxohexanenitrile

HRID 1261414Notes

Reaction equation

HRID 1261414 reaction equation
[C:1]([CH2:3][C:4]([OH:6])=O)#[N:2].C([Mg]Cl)(C)C.[Br:12][C:13]1[S:17][C:16]([C:18](=[O:24])[CH2:19][CH2:20]C(O)=O)=[CH:15][CH:14]=1.C1N=CN(C(N2C=NC=C2)=O)C=1>C1COCC1>[Br:12][C:13]1[S:17][C:16]([C:18](=[O:24])[CH2:19][CH2:20][C:4](=[O:6])[CH2:3][C:1]#[N:2])=[CH:15][CH:14]=1

Participants

6

Reactant 4

HCID 9740Cyanoacetic acidHCID 682631,1'-CarbonyldiimidazoleHCID 111846044-(5-Bromo-2-thienyl)-4-oxobutyric acidHCID 178418918HCID 178418918, compound

Product 1

HCID 582976466-(5-Bromothiophen-2-yl)-3,6-dioxohexanenitrileYield 69%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 2-cyanoacetic acid (13 g, 50 mmol) in THF (100 mL) was added dropwise i-PrMgCl (16 g, 250 mmol) at −78° C. for 1 h. A solution of 4-(5-bromothiophen-2-yl)-4-oxobutanoic acid (8A) and CDI (12 g, 74 mmol) in THF was added dropwise at −78° C. and the resultant mixture was stirred at −78° C. for 1 h and at room temperature for 1 h. The reaction mixture was quenched with saturated ammonium chloride (200 mL). The organic phase was separated, dried over Na2SO4, filtered, concentrated and purified by silica gel column chromatography (PE:EA=5:1) to afford 8B as a black oil (9.7 g, 69%).

Workup

  1. customThe reaction mixture was quenched with saturated ammonium chloride (200 mL)
  2. customThe organic phase was separated
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. custompurified by silica gel column chromatography (PE:EA=5:1)

Sources & evidence

ORD record
ord-e8efa9a86e674dd7ab1541ea4244283a
Source dataset
uspto-grants-2013_06
Patent number
US08470857B2

Reaction notes

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