1,3-Cyclohexadiene → Methyl 2-oxa-3-azabicyclo[2.2.2]oct-5-ene-3-carboxylate

HRID 1900619Notes

Reaction equation

HRID 1900619 reaction equation
[OH:1][NH:2][C:3](=[O:6])[O:4][CH3:5].[CH:7]1[CH2:12][CH2:11][CH:10]=[CH:9][CH:8]=1.I([O-])(=O)(=O)=O.C([N+](CCCC)(CCCC)CCCC)CCC.I([O-])(=O)(=O)=O.S(=O)(O)[O-].[Na+]>C(Cl)Cl>[CH3:5][O:4][C:3]([N:2]1[CH:9]2[CH2:10][CH2:11][CH:12]([CH:7]=[CH:8]2)[O:1]1)=[O:6]

Participants

7

Reactant 5

HCID 116051,3-CyclohexadieneHCID 164688Carbamic acid, hydroxy-, methyl esterHCID 167232Periodate2×HCID 2724292Tetrabutylammonium PeriodateHCID 23665763Sodium Bisulfite2×

Product 1

HCID 54430819Methyl 2-oxa-3-azabicyclo[2.2.2]oct-5-ene-3-carboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Conditions

Temperature
-10 °C

Procedure

A suspension of methyl N-hydroxycarbamate (17.81 g) in methylene chloride (350 ml) was cooled to about -13° C. (ice/acetone bath), and sequentially treated with 1,3-cyclohexadiene (14.24 g) and a suspension of tetrabutylammonium periodate (84.73 g) in methylene chloride (550 ml). The periodate suspension was added over a one hour period causing the temperature of the reaction to rise to a maximum of -5° C. After the addition of the periodate suspension was complete, the resulting reaction mixture was stirred at about -10° C. for three hours. A 10% sodium bisulfite solution (750 ml) was carefully added to the reaction mixture, while cooling in an ice/acetone bath. After about 45 minutes, the addition of the sodium bisulfite solution was complete. The organic phase was removed, washed with water (2×200 ml) and saturated sodium bicarbonate solution (2×500 ml). The organic phase was dried over sodium chloride, filtered, and concentrated in vacuo to give 180 g of the crude product. A solution of the crude product in methylene chloride was added to silica gel (200 g), and the resulting mixture evaporated to dryness. The title compound was isolated by flash silica-gel filtration, eluting with hexane/ethyl acetate (9:1, 2 L) and hexane/ethyl acetate (7:3, 500 ml). The fractions containing the title compound were combined, dried over sodium chloride and magnesium sulfate, filtered, and concentrated in vacuo to give 27.85 g of an oil. The oil was placed in a freezer to induce crystalization.

Workup

  1. customthe temperature of the reaction
  2. customto rise to a maximum of -5° C
  3. customthe resulting reaction mixture
  4. temperaturewhile cooling in an ice/acetone bath
  5. waitAfter about 45 minutes
  6. customThe organic phase was removed
  7. washwashed with water (2×200 ml) and saturated sodium bicarbonate solution (2×500 ml)
  8. dry with materialThe organic phase was dried over sodium chloride
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customto give 180 g of the crude product
  12. customthe resulting mixture evaporated to dryness

Sources & evidence

ORD record
ord-99e6c3e855c64a4c8b3fb3f50c84c505
Source dataset
uspto-grants-1996_11
Patent number
US05576323

Reaction notes

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