N'-hydroxy-2-methoxyethanimidamide → 5-(3-Methoxymethyl-1,2,4-oxadiazol-5-yl)-1-azabicyclo-[3.1.1]heptane oxalate salt

HRID 466815Notes

Reaction equation

HRID 466815 reaction equation
[CH3:1][O-:2].[Na+].[Na].[N:5]12[CH2:11][C:9]([C:12]([O:14]C)=[O:13])([CH2:10]1)[CH2:8][CH2:7][CH2:6]2.[CH3:16][O:17][CH2:18][C:19](=[N:21][OH:22])[NH2:20]>CO.C(O)(=O)C>[C:12]([OH:14])(=[O:13])[C:1]([OH:17])=[O:2].[CH3:16][O:17][CH2:18][C:19]1[N:20]=[C:12]([C:9]23[CH2:11][N:5]([CH2:10]2)[CH2:6][CH2:7][CH2:8]3)[O:22][N:21]=1

Participants

7

Reactant 4

HCID 4126736N'-hydroxy-2-methoxyethanimidamideHCID 5360545SodiumHCID 10942334Sodium MethoxideHCID 19814748Methyl 1-azabicyclo[3.1.1]hept-5-ylcarboxylate

Product 1

HCID 198147495-(3-Methoxymethyl-1,2,4-oxadiazol-5-yl)-1-azabicyclo-[3.1.1]heptane oxalate salt

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 887MethanolSolvent

Procedure

A stirred solution of sodium methoxide, prepared from 290 mg (0.012 mole) of sodium in methanol (20 ml), under nitrogen was treated with methyl 1-azabicyclo[3.1.1]hept-5-ylcarboxylate (D4, 300 mg, 0.0019 mole), methoxyacetamide oxime (D10, 1.0 g, 0.0097 mole) and powdered 3A molecular sieves (2.5 g). The mixture was heated under reflux for 3.5 h, then cooled in an ice bath and adjusted to pH 6 by the addition of glacial acetic acid. The mixture was concentrated in vacuo and the residue basified with concentrated potassium carbonate solution, then shaken with ethyl acetate (100 ml). The mixture was filtered and the organic layer separated, dried (Na2SO4) and concentrated in vacuo to leave a yellow oil. This material was chromatographed twice on basic alumina, each time eluting initially with ether then with 20% ethyl acetate/ether to eventually give a colourless oil (80 mg). This was converted to its oxalate salt and crystallised from acetone to give the title compound (E9 ) as a white solid (12%) m.p. 102°-104° C.

Workup

  1. temperatureThe mixture was heated
  2. temperatureunder reflux for 3.5 h
  3. temperaturecooled in an ice bath
  4. concentrationThe mixture was concentrated in vacuo
  5. filtrationThe mixture was filtered
  6. customthe organic layer separated
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated in vacuo
  9. customto leave a yellow oil
  10. customThis material was chromatographed twice on basic alumina
  11. washeach time eluting initially with ether

Sources & evidence

ORD record
ord-a983ff7935d24b0dbc3e19b46f31ef82
Source dataset
uspto-grants-1992_10
Patent number
US05157160

Reaction notes

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