Acetic Anhydride → 3-(Acetyloxy)-4-methyl-2-methylenepentanenitrile

HRID 2181394Notes

Reaction equation

HRID 2181394 reaction equation
[C:1](OC(=O)C)(=[O:3])[CH3:2].[OH:8][CH:9]([CH:14]([CH3:16])[CH3:15])[C:10](=[CH2:13])[C:11]#[N:12].[OH-].[Na+]>CN(C)C1C=CN=CC=1.O1CCCC1.C(OC)(C)(C)C.O>[C:11]([C:10](=[CH2:13])[CH:9]([O:8][C:1](=[O:3])[CH3:2])[CH:14]([CH3:16])[CH3:15])#[N:12]

Participants

8

Reactant 3

HCID 7918Acetic AnhydrideHCID 14798Sodium Hydroxide2×HCID 112404803-Hydroxy-4-methyl-2-methylenepentanenitrile

Product 1

HCID 152629853-(Acetyloxy)-4-methyl-2-methylenepentanenitrileYield 95.2%

Reagents, catalysts & solvents 4

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolvent3×HCID 8028TetrahydrofuranSolventHCID 15413tert-Butyl methyl etherSolvent2×

Conditions

Temperature
50 °C

Procedure

To a 500 mL, four-necked, round-bottom flask equipped with an overhead stirrer, a temperature probe, a reflux condenser, and a nitrogen inlet is charged acetic anhydride (40 mL, 0.45 mol). This solution is heated to 50° C. and a solution of 3-hydroxy-4-methyl-2-methylenepentanenitrile (50 g, 0.40 mol) and 4-(dimethylamino)pyridine (1.5 g) in tetrahydrofuran (25 mL) is added over 35 minutes. A temperature of 50° C. to 63° C. is maintained without external heating. After the addition is complete, the reaction mixture is heated at 60° C. for 75 minutes. The solution is cooled to 30° C. and the cooled reaction mixture is diluted with 30 mL of tert-butylmethyl ether (MTBE) and 25 mL of water. This mixture is cooled to 10° C. and a solution of 50% aqueous sodium hydroxide (37 g, 0.46 mol) diluted with 45 mL of water is added with cooling, such that the temperature is maintained at about 15° C. For the final pH adjustment, 50% aqueous sodium hydroxide 9.8 g (0.12 mol) is added dropwise to a final pH of 9.4. After adding 10 mL of water and 10 to 15 mL of MTBE, the reaction mixture is phased and separated. The upper organic product layer is separated and washed with 25 mL of brine, dried over magnesium sulfate, and concentrated in vacuo to provide 63.7 g (95%) of acetic acid 2-cyano-1-isopropyl-allyl ester as a pale yellow oil. Ethyl 3-cyano-5-methyl hex-3-enoate

Workup

  1. customTo a 500 mL, four-necked, round-bottom flask equipped with an overhead stirrer
  2. temperatureA temperature of 50° C. to 63° C. is maintained without external heating
  3. additionAfter the addition
  4. temperaturethe reaction mixture is heated at 60° C. for 75 minutes
  5. temperatureThe solution is cooled to 30° C.
  6. customthe cooled reaction mixture
  7. temperatureThis mixture is cooled to 10° C.
  8. additionis added
  9. temperaturewith cooling, such that the temperature
  10. temperatureis maintained at about 15° C
  11. customseparated
  12. customThe upper organic product layer is separated
  13. washwashed with 25 mL of brine
  14. dry with materialdried over magnesium sulfate
  15. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-28023fb5662840fbadc193a6807bf213
Source dataset
uspto-grants-2005_05
Patent number
US06891059B2

Reaction notes

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