Beta-Alanine → HCID 14539520, compound

HRID 1195324Notes

Reaction equation

HRID 1195324 reaction equation
[F:1][C:2]1[CH:16]=[CH:15][C:5]([C:6]([C:8]2[CH:13]=[CH:12][C:11]([F:14])=[CH:10][CH:9]=2)=O)=[CH:4][CH:3]=1.[C:17]([CH2:19][C:20]([O:22][CH2:23][CH3:24])=[O:21])#[N:18].C1C=CC=CC=1.NCCC(O)=O>O.C(O)(=O)C>[C:17]([C:19](=[C:6]([C:8]1[CH:13]=[CH:12][C:11]([F:14])=[CH:10][CH:9]=1)[C:5]1[CH:15]=[CH:16][C:2]([F:1])=[CH:3][CH:4]=1)[C:20]([O:22][CH2:23][CH3:24])=[O:21])#[N:18]

Participants

7

Reactant 4

HCID 239Beta-AlanineHCID 241BenzeneHCID 7764Ethyl cyanoacetateHCID 95824,4'-Difluorobenzophenone

Product 1

HCID 14539520HCID 14539520, compoundYield 56.3%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 962WaterSolvent2×

Procedure

A mixture of 20.0 g (92 mmoles) of 4,4'-difluorobenzophenone, 11.0 g (97 mmoles) of ethyl cyanoacetate in a mixed solvent of 100 mL of dry benzene and 20 mL of glacial acetic acid containing a catalytic amount of β-alanine (0.9 g) was refluxed with separation of water using a Dean-Stark water trap. Separation of water was rapid during the first 2 hours (0.4 mL aqueous layer collected) but slower afterward. Azeotropic distillation was continued for a period of 14 days. Analytical TLC eluted with 10% EtOAc in hexanes (v/v) (Merck plate, 0.25 mm Silica gel-F) showed two spots at Rf =0.2 (desired product) and at Rf =0.45 (4,4'-difluorobenzophenone starting material). Crude reaction mixture was washed with water (40 mL×2), and the combined aqueous washes were extracted with EtOAc (150 mL×2). The organic layers were combined, dried over MgSO4 and concentrated under reduced pressure to crystallize the product as pale cubic crystals. The crude product was collected, washed with 1:1 EtOAc in hexanes (v/v) then recrystallized from 8:1 (hexanes:ethyl acetate v/v) to give 16.2 g (56.3%) of analytical pure title compound; m.p.=114°-116° C.

Workup

  1. customSeparation of water
  2. customwas rapid during the first 2 hours (0.4 mL aqueous layer collected)
  3. distillationAzeotropic distillation
  4. washAnalytical TLC eluted with 10% EtOAc in hexanes (v/v) (Merck plate, 0.25 mm Silica gel-F)
  5. customCrude reaction mixture
  6. washwas washed with water (40 mL×2)
  7. extractionthe combined aqueous washes were extracted with EtOAc (150 mL×2)
  8. dry with materialdried over MgSO4
  9. concentrationconcentrated under reduced pressure
  10. customto crystallize the product as pale cubic crystals
  11. customThe crude product was collected
  12. washwashed with 1:1 EtOAc in hexanes (v/v)
  13. customthen recrystallized from 8:1 (hexanes:ethyl acetate v/v)

Sources & evidence

ORD record
ord-b2d60007794140089b796916b2c584eb
Source dataset
uspto-grants-1992_05
Patent number
US05110940

Reaction notes

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