Acetaldehyde → 2'-Methyl-1-azaspiro[bicyclo[2.2.2]octane-3,4'-[1,3]dioxolane]

HRID 2419033Notes

Reaction equation

HRID 2419033 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].O1CCC[CH2:8]1.[C:12]([C:16]1([OH:24])[CH:21]2[CH2:22][CH2:23][N:18]([CH2:19][CH2:20]2)[CH2:17]1)([O:14][CH3:15])=O.[OH-].[Na+].OCC1(O)C2CCN(CC2)C1.C(=O)C.B(F)(F)F.[OH-].[K+]>O1CCCC1.C(Cl)Cl.O.C(OCC)(=O)C>[CH3:8][CH:15]1[O:24][C:16]2([CH:21]3[CH2:22][CH2:23][N:18]([CH2:19][CH2:20]3)[CH2:17]2)[CH2:12][O:14]1

Participants

12

Reactant 7

HCID 177AcetaldehydeHCID 6356Boron trifluoride2×HCID 14797Potassium HydroxideHCID 14798Sodium HydroxideHCID 157498623-(Hydroxymethyl)-1-azabicyclo[2.2.2]octan-3-olHCID 20316852HCID 20316852, compoundHCID 21226445Aluminium lithium hydride

Product 1

HCID 30489442'-Methyl-1-azaspiro[bicyclo[2.2.2]octane-3,4'-[1,3]dioxolane]

Reagents, catalysts & solvents 4

HCID 962WaterSolvent2×HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred suspension of 17.5 g. lithium aluminum hydride in 100 ml dry tetrahydrofuran there was added during 1 hour a solution of 3-carbomethoxy-3-quinuclidinol tetrahydrofuran, 50 g in 100 ml. This was prepared according to Grob. Helv. Chim. Acta, 37, 1689 (1954). The reaction mixture was refluxed during 41/2 hours, treated with 20 ml ethyl acetate under nitrogen, then with water (17 ml) then with 15% aqueous sodium hydroxide (17 ml.), and again with water, 51 ml. The resulting mixture was filtered and the filtrate was evaporated under reduced pressure, leaving as residue a syrup, 35 g., comprising 3-hydroxymethyl-3-quinuclidinol. A quantity of 5 g. of this syrup was treated with 20 ml. acetaldehyde and 20 ml. of methylene chloride. The resulting emulsion was cooled to 0° C and treated under agitation with 20 ml boron trifluoride ethereate for 1 hour. The resulting mixture was then poured on water containing an excess of potassium hydroxide and stirred until a complete decomposition of boron trifluoride had taken place. The mixture was extracted with ether and the extract was subjected to evaporation under reduced pressure. The residue consisted of crude 2-methyl spiro (1,3-dioxolane-4,3') quinuclidine, B.P.=68°-72° at 0.2 mm-Hg , Rf on neutral alumina (ethyl acetate) = 0.6; M+ - 183. This product consists of a mixture of the two isomers wherein the methyl group is in one case in the cis-position (70%), the other in the trans-position (30%) respective to the nitrogen of the ring. The mixture was resolved into the two isomers by column chromatography on neutral alumina with ethyl acetate. The hydrochlorides of these were prepared by treatment of the two substances in dry acetone with gaseous hydrogen chloride, M.P. (cis-isomer) 233.8° (dec.); of the mixture : 234.2° (dec.).

Workup

  1. additionTo a stirred suspension of 17.5 g
  2. customThis was prepared
  3. temperatureThe reaction mixture was refluxed during 41/2 hours
  4. filtrationThe resulting mixture was filtered
  5. customthe filtrate was evaporated under reduced pressure
  6. customleaving as residue a syrup, 35 g
  7. additionof this syrup was treated with 20 ml
  8. extractionThe mixture was extracted with ether
  9. customthe extract was subjected to evaporation under reduced pressure
  10. additionThis product consists of a mixture of the two isomers wherein the methyl group
  11. customThe hydrochlorides of these were prepared by treatment of the two substances in dry acetone with gaseous hydrogen chloride, M.P. (cis-isomer) 233.8° (dec.)

Sources & evidence

ORD record
ord-c34c59d1251b414cb00d3823b8b06689
Source dataset
uspto-grants-1978_08
Patent number
US04104397

Reaction notes

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