Thionyl Chloride → 8-{3-[4-(2-Isopropoxy-phenyl)-piperazin-1-ylmethyl]-benzyl}-8-aza-spiro[4.5]decane-7,9-dione

HRID 1034142Notes

Reaction equation

HRID 1034142 reaction equation
[CH3:1][CH:2]([O:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[N:11]1[CH2:16][CH2:15][N:14]([CH2:17][C:18]2[CH:19]=[C:20]([CH:23]=[CH:24][CH:25]=2)[CH2:21][NH2:22])[CH2:13][CH2:12]1)[CH3:3].[CH2:26]1[CH2:30][C:29]2([CH2:37][C:35](=O)[O:34][C:32](=[O:33])[CH2:31]2)[CH2:28][CH2:27]1.S(Cl)(Cl)=O>C1(C)C=CC=CC=1>[CH3:3][CH:2]([O:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[N:11]1[CH2:16][CH2:15][N:14]([CH2:17][C:18]2[CH:19]=[C:20]([CH2:21][N:22]3[C:35](=[O:34])[CH2:37][C:29]4([CH2:30][CH2:26][CH2:27][CH2:28]4)[CH2:31][C:32]3=[O:33])[CH:23]=[CH:24][CH:25]=2)[CH2:13][CH2:12]1)[CH3:1]

Participants

5

Reactant 3

HCID 24386Thionyl ChlorideHCID 79743Cyclopentane-1,1-diacetic anhydrideHCID 10521066HCID 10521066, compound

Product 1

HCID 107198468-{3-[4-(2-Isopropoxy-phenyl)-piperazin-1-ylmethyl]-benzyl}-8-aza-spiro[4.5]decane-7,9-dione

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A solution of 3-[[1-[2-(1-methylethoxy)phenyl]-4-piperazinyl]methyl]-benzyl amine (2.50 g, 7.37 mmol), prepared as described above, 3,3-tetramethyleneglutaric anhydride (1.12 g, 6.66 mmol), and toluene (30 mL) was heated to reflux, cooled slightly, and treated with thionyl chloride (9.72 mL, 13.32 mmol). The resulting slurry was refluxed for 30 min, cooled and the solid collected by filtration. This material was partitioned between CH2Cl2 /3N NAOH and the organic layer was separated, dried, filtered and evaporated giving 8-[[3-[[1-[2-(1-methylethoxy)phenyl]-4-piperazinyl]methyl]phenyl]methyl]-8-azaspiro[4.5]decane-7,9-dione as a crude oil. The oil was converted to the maleate salt in i-PrOH. The isolated residue was converted back to the free base which was obtained as an oil (2.10 g). Chromatography of this material on flash silica using EtOAc/hexane of varying proportions gave an oil which was dissolved in ether and added to ethereal HCl causing formation of a solid. Filtration afforded 8-[[3-[[1-[2-(1-methylethoxy)phenyl]-4-piperazinyl]methyl]phenyl]methyl]-8-azaspiro[4.5]decane-7,9-dione dihydrochloride (0.94 g, 25%), m.p. 212°-216° C. (dec). 1H NMR and mass spectral analysis supported the assigned structure.

Workup

  1. temperaturewas heated
  2. temperatureto reflux
  3. temperaturecooled slightly
  4. temperatureThe resulting slurry was refluxed for 30 min
  5. temperaturecooled
  6. filtrationthe solid collected by filtration
  7. customThis material was partitioned between CH2Cl2 /3N NAOH
  8. customthe organic layer was separated
  9. customdried
  10. filtrationfiltered
  11. customevaporated

Sources & evidence

ORD record
ord-2597969e49ec44b5ab00fc40925b6fd7
Source dataset
uspto-grants-1994_05
Patent number
US05314885

Reaction notes

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