Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
  • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
  • C07D471/08—Bridged systems

Definitions

• the present invention relates to a process for the preparation of N, N'-dibenzyl bispidine.
• N, N'-dibenzylbispi ⁇ din can be prepared from N, N'-dibenzyl bispidone by reduction with hydrazine hydrate in triethylene glycol in the presence of potassium hydroxide.
• N, N'-dibenzylbispidone was obtained by reacting N-benzylpiperidone-4 with benzylamine.
• the intermediate product and the end product were purified by distillation in this process, the latter has only an insufficient purity, which is disadvantageous for the further conversion to the Ambasilide.
• the invention relates to a process for the preparation of N, N'-dibenzylbispidine, characterized in that N-benzylpiperidone is reacted with foritialin and benzylamine in the presence of acetic acid in a solvent at 50-100 ° C., the benzylamine , the acetic acid, the solvent and part of the benzylpiperidone are introduced at 50-100 ° C., then the remaining benzylpiperidone and part of the formalin are added, after which the reaction mixture is heated to reflux after addition of the remaining formalin and the acetate of the N, N'-dibenzyl bispidone obtained in this way is extracted from by-products after the methanol has been distilled off, and then the N, N'-dibenzyl bispidone is released and isolated, and then the N, N'-dibenzyl bispidone with hydrazine at 80- 200 ° C in one
• the benzylamine, the acetic acid and the solvent with some of the benzylpiperidone are introduced. 2-8 mol of acetic acid, preferably as a pure substance, are used per mol of benzylpiperidone.
• suitable solvents are methanol, ethanol, tetrahydrofuran, toluene and chlorinated hydrocarbons such as methylene chloride and chloroform.
• the benzylpiperidone is used in a total amount of 0.8 to 1.3 moles per mole of benzylamine in the reaction, the amount of benzylpiperidone initially charged being between 0 and 75%, is preferably 20-30%.
• the reaction is carried out at 50-100 ° C., after all the reactants have been brought together, the mixture is refluxed for a while.
• the solvent is stripped off in vacuo and the residue is taken up in water.
• the aqueous solution has been purified by extraction with a solvent such as toluene, ethers or chlorinated hydrocarbons, preferably methylene chloride
• the N, N'-dibenzyl bispidone is released from the salt and extracted with one of the solvents mentioned.
• the solvent preferably to n-propanol
• the N, N'-dibenzyl bispidone crystallizes out and is washed with a solvent such as n-propanol.
• the product obtained in this way which is over 99% pure, is reduced to N, N-dibenzylbispidine with hydrazine.
• the reaction is carried out in an ethylene glycol such as diethylene glycol or triethylene glycol. 2-3 moles of alkali metal hydroxide solution should be added per mole of bispidone.
• the molar ratio of bispidone: hydrazine is 1: 1 to 1: 5.
• the reaction temperature should be 50-100 ° C. at the start of the reaction and is then slowly increased to 170-200 ° C., a hydrazine-water mixture being distilled off. The reaction is complete after 20-24 hours.
• the product thus obtained is treated with hydrochloric acid and then with sodium hydroxide solution and extracted with toluene, an ether such as methyl tert-butyl ether or a chlorinated hydrocarbon such as methylene chloride or chlorotoluene. After removing the solvent, a very pure N, '-dibenzyl bispidine is obtained.
• the new production process for N, N'-dibenzylbispidine has the following advantages over the process known from DE-OS 24 28 792:
• the reaction volume can be reduced by half compared to the process known from DE-A 24 28 792. Furthermore, by using a gentle extraction process, the temperature-sensitive crude product can be freed from by-products to such an extent that a pure N, N'-dibenzyl bispidone is obtained.
• the method also makes it possible to exploit the scale-up, which is comparable to laboratory tests, and the two high-vacuum, high-temperature distillations, which are expensive in terms of process technology and energy, are saved. The crystals thus obtained are stable on storage.
• the purity of the .N, N'-dibenzyl bispidone is a prerequisite for its further processing into a high-purity N, N'-dibenzyl bispini, which does not require the high-vacuum distillation that was previously necessary or other cleaning processes can be directly implemented without isolation.
• the crude product was taken up in hot n-propanol and slowly cooled to 0 ° C.
• the crystallized material was suctioned off, washed and dried.
• the yield was 109 g of N, N'-dibenzyl bispidone. This corresponds to a yield of 55% based on the N-benzylpiperidone used.
• the purity was 99.8%.
• the reaction mixture was slowly heated to reflux (125 ° C). The temperature was raised to 190-200 ° C. and the hydrazine / water mixture was distilled off. The reaction was continued at this temperature until conversion was complete. After that was on

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• Chemical & Material Sciences (AREA)
• Organic Chemistry (AREA)
• Hydrogenated Pyridines (AREA)

Priority Applications (5)

Applications Claiming Priority (2)

Publications (1)

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Family Applications (1)

Country Status (11)

Cited By (1)

Citations (1)

• 1993
  • 1993-07-17 DE DE4324086A patent/DE4324086A1/de not_active Withdrawn
• 1994
  • 1994-06-28 EP EP94919667A patent/EP0710238A1/de not_active Withdrawn
  • 1994-06-28 HU HU9503859A patent/HU9503859D0/hu unknown
  • 1994-06-28 AU AU70733/94A patent/AU7073394A/en not_active Abandoned
  • 1994-06-28 CZ CZ9652A patent/CZ5296A3/cs unknown
  • 1994-06-28 CA CA002167406A patent/CA2167406A1/en not_active Abandoned
  • 1994-06-28 KR KR1019960700211A patent/KR960703913A/ko not_active Application Discontinuation
  • 1994-06-28 WO PCT/EP1994/002101 patent/WO1995002599A1/de not_active Application Discontinuation
  • 1994-06-28 JP JP7504314A patent/JPH09500119A/ja active Pending
  • 1994-06-28 PL PL94312609A patent/PL312609A1/xx unknown
  • 1994-07-01 MX MX9405030A patent/MX9405030A/es unknown

Patent Citations (1)

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