104224-63-7Relevant articles and documents
A high yield and pilot-scale process for the preparation of adapalene
Liu, Zhichang,Xiang, Jiannan
, p. 285 - 288 (2006)
Strategies that were adopted during the process development of adapalene to achieve a cost-effective commercial-scale synthesis are described herein. These included (1) the use of AcOH/H2SO4 to afford 2-(1-adamantyl)-4-bromophenol in quantitative yield; (2) the dimethyl sulfate methylation to enhance the yield of methylation to 95%; (3) direct conversion of the Grignard reagent into methyl 6-(3-(1-adamantyl)-4-methoxyphenyl)-2- naphthoate by the catalysis of both PdCl2-(PPh3) 2 and ZnCl2 in high yield; (4) the use of EDTA-disodium salt dihydrate to ensure the heavy metal's content within acceptable limits; (5) the use of toluene to simplify the original Chromatographic purification to recrystallization. The pilot-scale synthesis of adapalene is described in detail in the Experimental Section.
Ion-exchange-resin-catalyzed adamantylation of phenol derivatives with adamantanols: Developing a clean process for synthesis of 2-(1-adamantyl)-4- bromophenol, A key intermediate of adapalene
Wang, Nan,Wang, Ronghua,Shi, Xia,Zou, Gang
experimental part, p. 227 - 233 (2012/04/10)
A clean process has been developed for the synthesis of 2-adamantylphenol derivatives through adamantylation of substituted phenols with adamantanols catalyzed by commercially available and recyclable ion-exchange sulfonic acid resin in acetic acid.The sole byproduct of the adamantylation reaction,namely water,could be converted into the solvent acetic acid by addition of a slight excess of acetic anhydride during the work-up procedure,making the process waste-free except for regeneration of the ionexchange resin,and facilitating the recycling of the resin catalyst.The ion-exchange sulfonic acid resin catalyst could be readily recycled by filtration and directly reused at least ten times without a significant loss of activity.The key intermediate of adapalene,2-(1-adamantyl)-4-bromophenol,could be produced by means of this waste-free process.
S1P RECEPTORS MODULATORS AND THEIR USE THEREOF
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Page/Page column 80, (2010/04/30)
The invention relates to novel compounds that have S1P receptor modulating activity. Further, the invention relates to a pharmaceutical comprising at least one compound of the invention for the treatment of diseases and/or conditions caused by or associated with inappropriate S1P receptor modulating activity or expression, for example, autoimmune response. A further aspect of the invention relates to the use of a pharmaceutical comprising at least one compound of the invention for the manufacture of a medicament for the treatment of diseases and/or conditions caused by or associated with inappropriate S1P receptor modulating activity or expression such as autoimmune response.