Acetic Acid → Acetic acid, 2-cyano-2-(6-oxaspiro[4.5]dec-9-ylidene)-, methyl ester

HRID 76233Notes

Reaction equation

HRID 76233 reaction equation
[CH2:1]1[C:5]2([CH2:10][C:9](=O)[CH2:8][CH2:7][O:6]2)[CH2:4][CH2:3][CH2:2]1.[CH3:12][O:13][C:14](=[O:18])[CH2:15][C:16]#[N:17].C([O-])(=O)C.[NH4+].C(O)(=O)C>C1C=CC=CC=1.CCCCCC.CCOC(C)=O>[C:16]([C:15](=[C:9]1[CH2:10][C:5]2([CH2:4][CH2:3][CH2:2][CH2:1]2)[O:6][CH2:7][CH2:8]1)[C:14]([O:13][CH3:12])=[O:18])#[N:17]

Participants

8

Reactant 4

HCID 176Acetic AcidHCID 7747Methyl cyanoacetateHCID 517165Ammonium AcetateHCID 641064636-Oxaspiro[4.5]decan-9-one

Product 1

HCID 68313886Acetic acid, 2-cyano-2-(6-oxaspiro[4.5]dec-9-ylidene)-, methyl esterYield 87.8%

Reagents, catalysts & solvents 3

HCID 241BenzeneSolvent2×HCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 6-oxaspiro[4.5]decan-9-one (13.74 g, 89.1 mmol), methylcyanoacetate (9.4 ml, 106.9 mmol), ammonium acetate (1.79 g, 26.17 mmol) and acetic acid (1.02 ml, 17.8 mmol) in benzene (75 ml) was heated at reflux in a 250 ml round bottom flask equipped with a Dean-Stark and a reflux condenser. After 3 h, TLC (25% EtOAc in hexane, PMA stain) showed the reaction was completed. After cooling, benzene (50 ml) was added and the layer was separated, the organic was washed by water (120 ml) and the aqueous layer was extracted by CH2Cl2 (3×120 ml). The combined organic was washed with sat'd NaHCO3, brine, dried and concentrated and the residual was purified by flash chromatography (340 g silica gel column, eluted by EtOAc in hexane: 5% EtOAc, 2 CV; 5-25%, 14 CV; 25-40%, 8 CV) gave a mixture of E and Z isomers: methyl 2-cyano-2-[6-oxaspiro[4.5]decan-9-ylidene]acetate (18.37 g, 87.8% yield, m/z 236.0 [M+H]+ observed) as a clear oil.

Workup

  1. temperaturewas heated
  2. temperatureat reflux in a 250 ml round bottom flask
  3. customequipped with a Dean-Stark and a reflux condenser
  4. temperatureAfter cooling
  5. customthe layer was separated
  6. washthe organic was washed by water (120 ml)
  7. extractionthe aqueous layer was extracted by CH2Cl2 (3×120 ml)
  8. washThe combined organic was washed with sat'd NaHCO3, brine
  9. customdried
  10. concentrationconcentrated
  11. customthe residual was purified by flash chromatography (340 g silica gel column, eluted by EtOAc in hexane: 5% EtOAc, 2 CV; 5-25%, 14 CV; 25-40%, 8 CV)
  12. customgave
  13. additiona mixture of E and Z isomers

Sources & evidence

ORD record
ord-fbed925dc2f540648b3a1fc4c7cf1d4f
Source dataset
uspto-grants-2014_09
Patent number
US08835488B2

Reaction notes

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