- Purification method of 6-fluoro-3-(4-piperidyl)-1,2-benzoisoxazole hydrochloride
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The invention discloses a purification method of a risperidone intermediate 6-fluoro-3-(4-piperidyl)-1,2-benzoisoxazole hydrochloride as shown in a formula II, which is characterized by comprising the following steps: adding 6-fluoro-3-(4-piperidyl)-1,2-benzoisoxazole hydrochloride into ethanol, adding a certain amount of water, and carrying out heating reflux until the solution is clear to obtain the risperidone intermediate 6-fluoro-3-(4-piperidyl)-1,2-benzoisoxazole hydrochloride; and cooling the compound to a certain temperature for crystal growing, then cooling the mixture to -5 to 10 DEG C, and filtering and drying the mixture to obtain the crystal. According to the purification method of the 6-fluoro-3-(4-piperidyl)-1,2-benzoisoxazole hydrochloride, the dimer shown as the formula V can be effectively separated out, the purification yield is 85% or above, the chemical purity of a finished product can reach 99.9% or above, an amplification effect cannot be generated in large-scale production, and the process is stable.
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- Preparation method of 6-fluoro-3-(4-piperidyl)-1, 2-benzisoxazole hydrochloride
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The invention provides a preparation method of 6-fluoro-3-(4-piperidyl)-1, 2-benzisoxazole hydrochloride. The preparation method comprises the following steps of: dissolving 4-(2, 4-difluorobenzoyl)-piperidine hydrochloride into an alcohol solvent, adding hydroxylamine hydrochloride, then adding inorganic base, carrying out reaction for 5-72h at 20-65DEG C, then dropwise adding concentrated hydrochloric acid, performing cooling to 0-5DEG C, keeping the temperature for 1-3h, conducting filtering, and washing and filtering the obtained solid again to obtain the high-purity 6-fluoro-3-(4-piperidyl)-1, 2-benzoisoxazole hydrochloride. According to the method, alkali metal hydroxide is used as alkali, replaces triethylamine used as an oximation acid-binding agent, also is used as cyclization alkali, pollution of triethylamine to the environment is reduced, the reaction conditions are mild, the technological process is simple, and the cost is low.
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Paragraph 0017-0023
(2021/03/05)
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- Preparation method of risperidone
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The invention discloses a preparation method of risperidone, and belongs to the technical field of preparation methods for chemical medical intermediates. High-purity risperidone is prepared by performing oximation, cyclization and condensation reactions on 2,4- difluorophenyl-4,-piperidone methanone hydrochloride and 3-(2-chloroethyl)-6,7,8,9-tetrahydro-2-methyl-4H-pyridino-[1,2-a]pyridine-4-ketone as raw materials. The method disclosed by the invention has the advantages of adoption of relatively cheap and readily-available raw materials, easiness in operation, higher yield and higher industrial value.
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Paragraph 0030-0037
(2019/04/02)
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- Preparation method of iloperidone intermediate
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The invention relates to a preparation method of an iloperidone intermediate. The preparation method comprises the following steps of (1) adding potassium hydroxide into methyl alcohol, and adding (2,4-difluorophenyl)-(4-piperidyl)ketoxime hydrochloride; (2) heating, and reacting for 2 to 3h at the controlled temperature of 50 to 60 DEG C; (3) cooling to room temperature, adding anhydrous MgSO4, stirring for 0.8 to 1.2h, sucking and filtering, and performing vacuum concentration on filtrate; (4) adding acetone, stirring for 0.4 to 0.6h at the room temperature, filtering, dripping a saturated HCl methyl alcohol solution while stirring the filtrate, so as to adjust a pH (potential of hydrogen) value to 2-3, sucking and filtering, and drying, so as to obtain a white solid, wherein the water content of methyl alcohol is less than 0.5%.
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Paragraph 0041; 0042
(2017/07/19)
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- PIPERIDINE DERIVATIVES AND METHODS OF USE THEREOF
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The present invention relates to Compounds of Formula (I), compositions comprising the compounds, and methods of using the compounds to treat or prevent pain, diabetes, a diabetic complication, impaired glucose tolerance (IGT) or impaired fasting glucose (IFG) in a patient.
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- Process improvements for the preparation of kilo quantities of a series of isoindoline compounds
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A series of isoindoline analogues with either an indazole (HMR 2934, HMR 2651) or benzisoxazole (HMR 2543) appendage were prepared for the proposed treatment of psychiatric disorders such as obsessive compulsive disorder and attention deficit disorder. The isoindoline compounds were prepared by reduction of the corresponding phthalimides with LiAlH4. One compound was not chiral, and the other two required an enantioselective synthesis. The key step for these optically active analogues involved the coupling by an SN2 process of either a piperazynyl intermediate or a piperdinyl intermediate with methyl 3-benzyloxy-2-trifluoromethansulfonatopropionate. The products for these two analogues had >98% ee. Process improvements led to the multi-kilogram syntheses of each of these compounds.
- Watson, Timothy J.,Ayers, Timothy A.,Shah, Nik,Wenstrup, David,Webster, Mark,Freund, David,Horgan, Stephen,Carey, James P.
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p. 521 - 532
(2013/09/05)
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- 4-(1,2-benzisoxazolyl)piperidine antipsychotic agents
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Certain 1-substituted 4-(1,2-benzisoxazolyl)piperidine compounds exhibit neuroleptic activity and are useful in the treatment of psychosis and anxiety.
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- Synthesis and Neuroleptic Activity of 3-(1-Substituted-4-piperidinyl)-1,2-benzisoxazoles
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The synthesis of a series of 3-(1-substituted-4-piperidinyl)-1,2-benzisoxazoles is described.The neuroleptic activity of the series was evaluated by utilizing the climbing mice assay and inhibition of spiroperidol binding.Structure-activity relationships were studied by variation of the substituent on the benzisoxazole ring with concomitant variation of four different 1-piperidinyl substituents.Maximum neuroleptic activity was realized when there was a 6-fluoro substituent on the benzisoxazole ring.The 1-piperidinyl substituent appeared less significant, although in most cases, the (1,3-dihydro-2-oxo-2H-benzimidazol-1-yl)propyl group imparted maximum potency.The most potent compound in both assays was 6-fluoro-3--4-piperidinyl>-1,2-benzisoxazole (11b).
- Strupczewski, Joseph T.,Allen, Richard C.,Gardner, Beth Ann,Schmid, Blaine L.,Stache, Ulrich,et al.
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p. 761 - 769
(2007/10/02)
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- 3-(4-Piperidyl)-1,2-benzisoxales
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Novel 3-(4-piperidyl)-1,2-benzisoxazoles, intermediates and processes for the preparation thereof, and methods for alleviating pain utilizing compounds or compositions thereof are disclosed.
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