Water → 4-(4-Chlorophenyl)-3-oxobutanenitrile

HRID 1808250Notes

Reaction equation

HRID 1808250 reaction equation
C([Mg]Cl)(C)C.[C:6]([CH2:8][C:9]([OH:11])=O)#[N:7].[Cl:12][C:13]1[CH:18]=[CH:17][C:16]([CH2:19]C(O)=O)=[CH:15][CH:14]=1.C1N=CN(C(N2C=NC=C2)=O)C=1.O>C1COCC1.CC(O)=O>[Cl:12][C:13]1[CH:18]=[CH:17][C:16]([CH2:19][C:9](=[O:11])[CH2:8][C:6]#[N:7])=[CH:15][CH:14]=1

Participants

8

Reactant 5

HCID 962WaterHCID 9740Cyanoacetic acidHCID 15880(4-Chlorophenyl)acetic acidHCID 682631,1'-CarbonyldiimidazoleHCID 178418918HCID 178418918, compound

Product 1

HCID 509888474-(4-Chlorophenyl)-3-oxobutanenitrileYield 82.1%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolvent2×HCID 8028TetrahydrofuranSolvent3×

Procedure

2 M of isopropylmagnesium chloride in THF (300 mL) was added to a −78° C. solution of cyanoacetic acid (28.3 g, 333 mmol) in anhydrous THF (600 mL, 7000 mmol). After 1 h, a solution of 4-chlorophenylacetic acid (20 g, 100 mmol) and N,N-carbonyldiimidazole (21.7 g, 134 mmol) in anhydrous THF (200 mL, 2000 mmol) was added. The reaction mixture was warmed to rt. After 16 h, the reaction mixture was poured into water (1 L, 60000 mmol). The mixture was adjusted to pH 4 with glacial AcOH. Gas evolution was evident during addition of the AcOH. The mixture was concentrated in vacuo to remove the THF (in 1 L portions). The product crystallized from the aqueous portions. The solid was collected by filtration, washing with water. Dried under vacuum to afford the product as a fluffy light orange-yellow solid (15.89 g, 60%).

Workup

  1. waitAfter 16 h
  2. concentrationThe mixture was concentrated in vacuo
  3. customto remove the THF (in 1 L portions)
  4. customThe product crystallized from the aqueous portions
  5. filtrationThe solid was collected by filtration
  6. washwashing with water
  7. customDried under vacuum

Sources & evidence

ORD record
ord-6770707514b94ddfa110310bf567190b
Source dataset
uspto-grants-2013_01
Patent number
US08357711B2

Reaction notes

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