Acetic Acid → (+/-) Z 3-(Ethoxycarbonylmethylene)-1-azabicyclo-[2.2.1]heptane oxalate salt

HRID 129825Notes

Reaction equation

HRID 129825 reaction equation
[CH3:1][C:2](C)([O-])C.[K+].[N:7]12[CH2:13][CH:10]([CH2:11][CH2:12]1)[C:9](=O)[CH2:8]2.[C:15]([OH:18])(=[O:17])[CH3:16].[C:19]([OH:24])(=[O:23])[C:20]([OH:22])=[O:21]>CN(C=O)C.CCOCC.CO>[C:19]([OH:24])(=[O:23])[C:20]([OH:22])=[O:21].[CH2:1]([O:17][C:15](/[CH:16]=[C:9]1\[CH2:8][N:7]2[CH2:13][CH:10]\1[CH2:11][CH2:12]2)=[O:18])[CH3:2]

Participants

8

Reactant 4

HCID 176Acetic AcidHCID 971Oxalic AcidHCID 108554071-Azabicyclo[2.2.1]heptan-3-oneHCID 23665647Potassium tert-butoxide

Product 1

HCID 19370568(+/-) Z 3-(Ethoxycarbonylmethylene)-1-azabicyclo-[2.2.1]heptane oxalate salt

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent2×

Procedure

Triethylphosphonoacetate (2.69 g, 0.012 moles) in dry DMF (10 ml) was treated with potassium t-butoxide (1.59 g, 0.013 moles) at 0° C. with continuous stirring under an atmosphere of nitrogen. After 30 minutes (±)1-azabicyclo [2.2.1]heptan-3-one (D6, 1.11 g, 0.01 moles) in DMF (10 ml) was added at 0° C. and the stirred solution allowed to warm to room temperature over a period of 30 min. After standing at room temperature for lh the reaction was neutralised with acetic acid and concentrated in vacuo to a gum. The gum was then partitioned between aqueous potassium carbonate and chloroform. The chloroform solution was separated and concentrated in vacuo to a gum. Kugelrohr distillation in vacuo afforded a colourless oil b.pt 200° C. at 0.5 mm. The oil was dissolved in ether (20 ml) and treated with oxalic acid (900 mg) in methanol (2 ml). The title compound oxalate salt (D1) slowly crystallised out. Recrystallisation from methanol-ether afforded the pure title compound free from the E isomer as needles (D1) (2.13 g; 78%). m.p. 140°-150° C.

Workup

  1. customAfter standing at room temperature for lh
  2. concentrationconcentrated in vacuo to a gum
  3. customThe gum was then partitioned between aqueous potassium carbonate and chloroform
  4. customThe chloroform solution was separated
  5. concentrationconcentrated in vacuo to a gum
  6. distillationKugelrohr distillation in vacuo
  7. customafforded a colourless oil b.pt 200° C. at 0.5 mm
  8. customThe title compound oxalate salt (D1) slowly crystallised out
  9. customRecrystallisation from methanol-ether

Sources & evidence

ORD record
ord-b279f2892c784b06955dd12383fbfa16
Source dataset
uspto-grants-1995_11
Patent number
US05470859

Reaction notes

Loading…