Benzonitrile → HCID 68648017, compound

HRID 1161758Notes

Reaction equation

HRID 1161758 reaction equation
[CH3:1][C:2]1[CH:6]=[C:5]([CH2:7][C:8]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[O:9])[O:4][N:3]=1.[CH3:16][C:17]1[CH:21]=[C:20]([CH3:22])[O:19]N=1.[Li][CH2:24]CCC.[C:28](#[N:35])C1C=CC=CC=1>C1COCC1>[OH:22][C:20]1[CH:19]=[CH:24][C:16]([NH:35][CH:28]=[C:7]([C:5]2[O:4][N:3]=[C:2]([CH3:1])[CH:6]=2)[C:8]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[O:9])=[CH:17][CH:21]=1

Participants

6

Reactant 4

HCID 7505BenzonitrileHCID 93123,5-DimethylisoxazoleHCID 109545992-(3-Methyl-5-isoxazolyl)-1-phenyl-1-ethanoneHCID 178418339Butyllithium

Product 1

HCID 68648017HCID 68648017, compoundYield 25%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

2-(3-Methyl-5-isoxazolyl)-1-phenyl-1-ethanone. To a solution of 8.73 g (90 mmol) of 3,5-dimethylisoxazole in 100 mL of THF at −70° C. under N2 was added dropwise a 1.55 M solution of nBuLi in hexanes (56.4 mL, 87 mmol). After stirring cold for 30 m, a solution of 10.3 g (100 mmol) of benzonitrile in 50 mL of THF was added dropwise. The reaction was allowed to warm to rt and stirred overnight. The solvent was removed in vacuo and the residue was partitioned between EtOAc and water. The organic layer was separated, washed with an aq. 1N HCl solution, dried (Na2SO4), filtered and conc. to dryness. Purification by silica gel chromatography (1:1 EtOAc/hexanes) followed by recrystallization gave the desired product as colorless crystals, mp 75-77° C. (25% yield; lit, Hicks, M. J. and Tong, Y. C., U.S. Pat. No. 5,338,856, Aug. 16, 1994, mp 73-74° C.). 1H NMR (CDCl3, 400 MHz) δ 8.00 (d, 2H), 7.60 (m, 1H), 7.50 (d, 2H), 6.15 (s, 1H), 4.40 (s, 2H), 2.30 (s, 3H); TOF MS ES+ m/z 202 (MH+).

Workup

  1. stirringstirred overnight
  2. customThe solvent was removed in vacuo
  3. customthe residue was partitioned between EtOAc and water
  4. customThe organic layer was separated
  5. washwashed with an aq. 1N HCl solution
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered and conc. to dryness
  8. customPurification by silica gel chromatography (1:1 EtOAc/hexanes)
  9. customfollowed by recrystallization

Sources & evidence

ORD record
ord-6ea240dd4e12411caecdd28f674a88eb
Source dataset
uspto-grants-2010_10
Patent number
US07820663B2

Reaction notes

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