Water → HCID 89853727, compound

HRID 931076Notes

Reaction equation

HRID 931076 reaction equation
[H-].[Na+].[O:3]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]#[N:10])=[N:4]1.Br[CH2:12][CH2:13]Br.O>CN(C)C=O>[O:3]1[CH:7]=[CH:6][C:5]([C:8]2([C:9]#[N:10])[CH2:13][CH2:12]2)=[N:4]1

Participants

6

Reactant 4

HCID 962WaterHCID 78391,2-DibromoethaneHCID 24758Sodium hydrideHCID 147657713-cyanomethylisoxazole

Product 1

HCID 89853727HCID 89853727, compoundYield 83.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a suspension of sodium hydride (136 mg, 5.39 mmol) in N,N-dimethylformamide (5 mL) was added a solution of 2-(isoxazol-3-yl)acetonitrile (233 mg, 2.16 mmol) in N,N-dimethylformamide (2.5 mL) at 0° C. After the addition, the mixture was warmed to room temperature and stirred for 1 h. The mixture was cooled to 0° C. and 1,2-dibromoethane (0.3 mL, 3.48 mmol) was added. The reaction mixture was stirred at 0° C. for 4 h. Water was added to the mixture. The mixture was extracted with ethyl acetate (3×). The combined organics were washed with water, washed with aqueous hydrochloric acid (1N), washed with aqueous sodium bicarbonate and brine. The organics were dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was dissolved with dichloromethane and washed with aqueous lithium chloride solution (10%). The organics were dried over sodium sulfate, filtered and concentrated under reduced pressure and dried under a stream of nitrogen to afford 1-(isoxazol-3-yl)cyclopropanecarbonitrile (243 mg). 1H NMR (500 MHz, CDCl3) δ 1.71-1.76 (m, 2H), 1.79-1.83 (m, 2H), 6.51 (s, 1H), 8.40 (s, 1H). The material was used without further purification.

Workup

  1. additionAfter the addition
  2. temperatureThe mixture was cooled to 0° C.
  3. stirringThe reaction mixture was stirred at 0° C. for 4 h
  4. extractionThe mixture was extracted with ethyl acetate (3×)
  5. washThe combined organics were washed with water
  6. washwashed with aqueous hydrochloric acid (1N)
  7. washwashed with aqueous sodium bicarbonate and brine
  8. dry with materialThe organics were dried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. dissolutionThe residue was dissolved with dichloromethane
  12. washwashed with aqueous lithium chloride solution (10%)
  13. dry with materialThe organics were dried over sodium sulfate
  14. filtrationfiltered
  15. concentrationconcentrated under reduced pressure
  16. customdried under a stream of nitrogen

Sources & evidence

ORD record
ord-8361f06a619a4289b00bd00f504cb175
Source dataset
uspto-grants-2016_03
Patent number
US09296745B2

Reaction notes

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