3-Butenoic acid → 3-(4-Cyanophenyl)isoxazolin-5-ylacetic acid

HRID 2394376Notes

Reaction equation

HRID 2394376 reaction equation
[C:1]([C:3]1[CH:11]=[CH:10][C:6]([CH:7]=[N:8][OH:9])=[CH:5][CH:4]=1)#[N:2].[CH:12]([CH2:14][C:15]([OH:17])=[O:16])=[CH2:13].Cl[O-].[Na+]>O1CCCC1>[C:1]([C:3]1[CH:11]=[CH:10][C:6]([C:7]2[CH2:13][CH:12]([CH2:14][C:15]([OH:17])=[O:16])[O:9][N:8]=2)=[CH:5][CH:4]=1)#[N:2]

Participants

5

Reactant 3

HCID 327433-Butenoic acidHCID 52147424-Cyanobenzaldehyde oximeHCID 23665760Sodium Hypochlorite

Product 1

HCID 110425463-(4-Cyanophenyl)isoxazolin-5-ylacetic acidYield 44.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4-cyanobenzaldoxime (see Ex 2) (312 g, 2.13 mol) in tetrahydrofuran (3 L) at room temperature was added vinylacetic acid (552 g, 6.41 mol). The yellow solution was cooled in an ice bath and sodium hypochlorite solution (5200 mL)was added in a dropwise fashion over 2 h. After stirring overnight at room temperature the reaction was quenched with a 5% citric acid solution and diluted with 200 mL ether. The layers were separated and the aqueous acidified to pH 4 using citric acid. The acid layer was washed twice with 200 mL ether, the ether layers combined and extracted with saturated sodium bicarbonate solution. After acidifying the basic layer with citric acid, the product was extracted into 400 mL ether. The organic phase was washed three times with 150 mL water, once with brine, dried (MgSO4) and concentrated to give 220 g of 3-(4-cyanophenyl)isoxazolin-5-ylacetic acid as a white solid. Recrystallization from 25% water/ethanol yielded 165 g of analytically pure material; 1H NMR (300 MHz, CDCl3) δ 7.77-7.76 (d, J=1.8 Hz, 2H), 7.72-7.71 (d, J=1.8 Hz, 2H), 5.22-5.14 (m, 1H), 3.63-3.54 (dd, J=10.6 Hz, 16.8 Hz, 1H), 3.19-3.11 (dd, J=7.3 Hz, 16.8 Hz, 1H), 3.00-2.93 (dd, J=6.2 Hz, 16.5 Hz, 1H), 2.79-2.72 (dd, J=7.3 Hz, 16.5 Hz, 1H); IR (KBr): 3202, 2244, 1736, 1610, 1432, 1416, 1194, 1152, 928, 840, 562 cm-1. Anal. Calcd for C12H10N2O3 : C, 62.61; H, 4.38; N, 12.17. Found: C, 62.37; H, 4.47; N, 11.71.

Workup

  1. temperatureThe yellow solution was cooled in an ice bath
  2. customwas quenched with a 5% citric acid solution
  3. additiondiluted with 200 mL ether
  4. customThe layers were separated
  5. washThe acid layer was washed twice with 200 mL ether
  6. extractionextracted with saturated sodium bicarbonate solution
  7. extractionthe product was extracted into 400 mL ether
  8. washThe organic phase was washed three times with 150 mL water
  9. dry with materialonce with brine, dried (MgSO4)
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-65be2ef34d914d199db149c77ecaa26d
Source dataset
uspto-grants-1998_09
Patent number
US05811441

Reaction notes

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