3607-34-9Relevant articles and documents
Refining method of doxepin hydrochloride
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Paragraph 0025-0026; 0031-0032; 0037-0038, (2021/05/01)
The invention belongs to the field of medicine synthesis, and relates to a refining method of doxepin hydrochloride. The refining method of doxepin hydrochloride comprises the following steps: adding a doxepin hydrochloride crude product into water, adjusting the pH value with alkali liquor, extracting with dichloromethane, and spin-drying an organic phase to obtain free doxepin. The method comprises the following steps: dissolving free doxepin in a mixed solvent of diethyl ether and ethanol, adding maleic acid in a controlled temperature range, and stirring to separate out doxepin maleate; adding doxepin maleate into water, adjusting the pH value with alkali liquor, extracting with dichloromethane, and spin-drying an organic phase to obtain free doxepin; dropwise adding isopropyl ether hydrogen chloride into the free doxepin, stirring and crystallizing to obtain doxepin hydrochloride. The Z-configuration doxepin hydrochloride content of the product obtained by the method is 17%-18.5%.
Synthesis method of doxepin hydrochloride
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Paragraph 0059-0074; 0119-0154, (2021/11/03)
The invention relates to a synthetic method of doxepin hydrochloride. The method comprises the following steps: (1) phosphites react with 3 - chlorine -1 - (N, N - dimethyl) propylamine to obtain 3 - (N, N - dimethyl) propyl phosphate, or a salt thereof with hydrochloric acid to obtain 3 - (N, N - dimethyl) propyl phosphate hydrochloride. (2) Reaction of 3 - (N, N -dimethyl) propyl phosphate or its hydrochloride with 6, 11 -dihydrodibenzo [b, e] oxepin -11 - ketone under strong base conditions Wittig to obtain doxorubicin. (3) The multi-plug is subjected to salt formation reaction with hydrochloric acid to prepare the doxorubicin hydrochloride. In 1st-step reaction step, the yield of the alkyl phosphate product prepared by adopting the reaction is high, thereby ensuring the yield and purity of the final product hydrochloride. Compared with the prior art, the method has the advantages of simple process, low production cost, less process steps and the like.
Iron(II) promoted direct synthesis of dibenzo[b,e]oxepin-11(6H)-one derivatives with biological activity. A short synthesis of doxepin
Scoccia, Jimena,Castro, M. Julia,Faraoni, M. Belén,Bouzat, Cecilia,Martín, Víctor S.,Gerbino, Darío C.
, p. 2913 - 2922 (2017/04/26)
A novel and efficient synthesis of dibenzo[b,e]oxepin-11(6H)-ones by direct intramolecular ortho-acylation from readily available 2-(phenoxymethyl)benzoic acids was developed. The method takes advantage of a newly developed cooperative system consisting of sustainable FeCl2 and Cl2CHOCH3 as the key components. This methodology is compatible with a wide variety of functional groups in good to excellent yields and high regioselectivity. The synthetic application of new protocol was extended to the synthesis of known tricyclic drug doxepin as well as a small library of oxepin based derivatives. For the first time, the obtained dibenzo[b,e]oxepinone derivatives were evaluated for their biological activities on the free-living nematode Caenorhabditis elegans as an effective and cost-efficient model system for anthelmintic discovery.