Intermediate substance

In its present form, intermediate 12 is not a viable substrate for the crucial Dieckmann condensation it must undergo prior epimerization at C-16. When intermediate 12 is treated with sodium methoxide in hot methanol, enolization at C-16 occurs and an equilibrium is established between 12 and a diastereomeric substance, intermediate 11. Once formed, 11 can either revert back to 12 through the planar enolate form, or it can participate in a productive cyclization reaction to give a new six-membered ring. Under these conditions, the desired transformations take place with exceptional facility to give, after acidification of the reaction medium, enol ester 10. 

Scheme 21 presents the successful sequence of reactions that solved the remaining two problems and led to the completion of the synthesis of cobyric acid. Exposure of 96 to concentrated sulfuric acid for one hour brings about a clean conversion of the nitrile grouping to the corresponding primary amide grouping. The stability of die corrin nucleus under these rather severe conditions is noteworthy. This new substance, intermediate 97, is identified as cobyrinic acid abcdeg hexamethylester f amide and it is produced along with a very similar substance which is epimeric to 97 at C-13. The action of sulfuric acid on 96 produces a diastereomeric... 

Type II Drug substance, drug substance intermediate, and materials used in their preparation, or drug product... 

A move to a different manufacturing site, except one used to manufacture or process a drug substance intermediate, when the new manufacturing site has never been inspected by FDA for the type of operation that is being moved or the move results in a restart at the new manufacturing site of a type of operation that has been discontinued for more than two years. 

A move to a different manufacturing site for the manufacture or processing of drug substance intermediates, other than the final intermediate. 

The basic requirements for a type II DMF submission for an API, a drug substance intermediate, and any material used in the preparation of a drug product consists of the following elements ... 

Type II Drug Substance, Drug Substance Intermediate, and Material Used in Their Preparation, or Drug Product... 

Indications of further complexities in the coherent type of surface films were found by Langmuir, and have been further investigated by Labrouste,1 Adam, and others. It is now well established that there frequently exists a coherent, expanded state in insoluble surface films of fatty substances, intermediate in area between the very closely packed condensed films, and the gaseous films in which the molecules move about independently on the surface. This most interesting type of film will be discussed in 18 and 19. 

It is often convenient to number the head of the series of substances (intermediates) with 1 and the tail with zero. 

Figure 21-10. Enantiomeric separation of a drag substance intermediate on a chiral stationary phase [semipreparative column (34-cm x 10-cm i.d.) containing 1.8kg of CSP] 5 g of racemate is injected every 4 minutes onto the colnmn this is the identical time interval for the peak widths of both enantiomers after elntion.

Chemistry Reviews of DMF s for Drug Substances/Intermediates (DSI), Manual of Policies and Procedures. Food and Drug Administration, Center for Drug Evaluation and Research,... 

Use Chlorination of organic substances, intermediate, production of pure metal. 

Most process steps involved in the manufacture of drug substances, intermediates, and regulatory starting materials occur in the presence of a solvent or combination of solvents. Depending on the manufacturing process and regulatory requirements, these materials may be tested for the amount of solvent(s) present in the sample by the compendial methods. 

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