Yield purity

Process. In each of the systems discussed above there is a need to form crystals, to cause the crystals to grow, and to separate the crystals from residual Hquid. There are various ways to accomplish these objectives lea ding to a multitude of processes that are designed to meet requirements of product yield, purity, and, uniquely, crystal size distribution. 

Entry Isatin Amino acid Product Yield (%) Purity (%)... 

Entry Batch size Reaction temp., time Process time Isol. yield Purity Remarks... 

Entry Boronic Acid Halide Yield% (Purity%)... 

Process validation entails firstly the definition of both the critical and non-critical parameters. Qnce they are defined, emphasis can be directed to designing a program to validate these parameters. Some established steps involve the evaluation of process consistency over at least three batches, via the consideration of the processing steps and yield and comparing these with predetermined specifications. Some input parameters that may be considered as critical are temperature, flow rate, and stirring speed, and they are varied and checked against output variables such as yield, purity, and crystallization rate. 

ARO reaction with phenols and alcohols as nucleophiles is a logical extension of HKR of epoxides to synthesize libraries of stereochemically defined ring-opened products in high optical purity. To this effect Annis and Jacobsen [69] used their polymer-supported Co(salen) complex 36 as catalyst for kinetic resolution of epoxides with phenols to give l-aiyloxy-2-alcohols in high yield, purity and ee (Scheme 17). Conducting the same reaction in the presence of tris(trifluoromethyl)methanol, a volatile, nonnucleophilic protic acid additive accelerates KR reaction with no compromise with enantioselectivity and yield. Presumably the additive helped in maintaining the Co(III) oxidation state of the catalyst. 

Although the imidazolidinone catalysts used within these transformations are simple, cheap, readily accessible and in some cases recyclable using acid/base extraction, considerable efforts have been made to examine alternative methods to separate and recycle the catalyst with good success. Examination of the structure of imidazolidinone 22 shows two convenient points for the introduction of a polymer or fluorous support, R and R, both of which have been examined (Fig. 4). Curran has shown that identical reactivity, diastereoselectivity and enantioselectivity can be obtained using a fluorous tag (23) [53]. The catalyst can easily be recovered and recycled using F-SPE with excellent yield, purity and levels of activity. Polymer- (24) and silica-supported (25) imidazolidinones reported by Pihko [54] (R substitution)... 

The free base 13 is obtained by stirring with sodium acetate in MTBE. Benzylation by treatment with a mild acid and p-methoxybenzyl alcohol provides 14 (Emert et al., 1977 Henneus et al., 1996). The initial conditions for the asymmetric addition of the lithium acetylide to the trifluoroketone appear in an earlier Merck paper (Thompson et al., 1993, 1996). Optimization of these conditions, which include some elaborate NMR studies (Thompson et al., 1998) and key scale-up experiments, provides a reliable and scaleable procedure to install the stereocenter in high yield, purity, and enantioselectivity (Scheme 6.3). n-Butyllithium (or w-hexyllithium, minimum four equivalents) is added to a solution of (lR,25)-A-pyrrolidinylnorephedrine (Corey and Cimrich, 1994) (two equivalents) and cyclopropylacetylene (two equivalents) at — 10°C and the reaction is allowed to warm to 0°C. These conditions are critical to establish the chiral complex that is responsible for the high enantioselectivity. This solution is cooled below — 50°C, and trifluoroketone 14 in THE is added and stirred for about 1 h at this temperature before... 

A critical appraisal of all synthetic routes of CL-20 vis-a-vis yield, purity and ease of scaling-up had been carried out by Sanderson and coworkers [126] and the gist of their conclusions is ... 

In spite of the simplicity of PTC procedures, they usually assure higher yields, purity, and selectivity of the desired products formation. 

Loaded resin Cleavage conditions Product, yield (purity) Ref. 

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