Mother liquor samples

This technique is quite frequently used to improve the ee of almost enantiomerically pure samples, since, in general, crystals are most stable if they consist either of a single enantiomer or of a racemic mixture. Recrystallization of samples with ees greater than about 85% has a good chance of improving the ee of the sample (the minor enantiomer remaining in the mother liquors). Samples with... 

A bulk lot sample of drug substance contained an unknown process-related impurity at 0.4% in case study B.7. To meet project time lines, it was necessary to identify the impurity. Mass spectral data indicated that the impurity had a molecular weight of M+12 (compared to the parent). LC/MS/ MS data indicated that the change was located in the sugar portion of the molecule. Isolation and NMR analysis was required to provide more structural information on the impurity. This again was a process-related impurity not observed in forced degradation studies therefore, effort was placed on finding an enriched mother liquor sample. 

It is clear that repeated recrystallisation will rapidly leave B entirely in the mother-liquors, and thus provide a pure sample of A. 

The theory underlying the removal of impurities by crystaUisation may be understood from the following considerations. It is assumed that the impurities are present in comparatively small proportion—usually less than 5 per cent, of the whole. Let the pure substance be denoted by A and the impurities by B, and let the proportion of the latter be assumed to be 5 per cent. In most instances the solubilities of A (SJ and of B (/Sb) are different in a particular solvent the influence of each compound upon the solubility of the other will be neglected. Two cases will arise for an3 particular solvent (i) the impurity is more soluble than the compound which is being purified (/Sg > SA and (ii) the impurity is less soluble than the compound Sg < S ). It is evident that in case (i) several recrystallisations will give a pure sample of A, and B will remain in the mother liquors. Case (ii) can be more clearly illustrated by a specific example. Let us assume that the solubility of A and 5 in a given solvent at the temperature of the laboratory (15°) are 10 g. and 3 g. per 100 ml. of solvent respectively. If 50 g. of the crude material (containing 47 5 g. of A and 2-5 g. of B) are dissolved in 100 ml. of the hot solvent and the solution allowed to cool to 15°, the mother liquor will contain 10 g. of A and 2-5 g. (i.e., the whole) of B 37-5 g. of pure crystals of A will be obtained. 

The ether extract is evaporated to dryness to give about 500 mg of a crude product. From the ether solution there is obtained about 290 mg of yellow crystals, MP 220° to 236°C which is 17a,20,20,21-bis(methylenedioxy)-11 (3-formyloxy-2-hydroxy-methylene-6,16a-di-methyl-4,6-pregnadiene-3-one. The analytical sample is recrystallized from ethyl acetate and has a melting point of 249° to 255°C, [oIq -217°, I R 5.81 and 8.37 ji. From the mother liquor is obtained about 127 mg of 17a,20,20-21-bis(methylenedioxy)-11(3-hydroxy-2-hydroxymethylene-6,16a-dimethyl-4,6-pregnadiene-3-one. The analytical sample is recrystallized from ether and has a melting point of 200° to 204°C, [alo -197°, IR 6.05 to 6.2 and 6.4 jd. 

The above crude bromohydrin was mixed with 2.5 grams of potassium acetate and 60 cc of acetone and refluxed for 6 hours, at the end of which the acetone was distilled, water was added to the residue and the product was extracted with methylene chloride. The extract was washed with water, dried over anhydrous sodium sulfate and the solvent was evaporated. Recrystallization of the residue from methanol furnished 800 mg of the 16,21-diacetate of 6o-fluoro-9(3,11(3-oxido-A -pregnene-16o,l7a,2l-triol-3,20-dione with MP 120° to 124°C by chromatography of the mother liquors on silica gel there was obtained 180 milligrams more of the same compound with MP 117° to 119°C. The analytical sample was obtained by recrystallization from methanol it showed MP 125° to 127°C. 

It is dissolved in hot methanol and heated on the steam bath with 10% methanolic potassium hydroxide solution (15.8 ml) for 10 minutes. Then more potassium hydroxide solution (2 ml) is added, the solution is cooled and on dilution with water a solid (II), MP 245° to 255°C, is obtained. A second crop is obtained from the mother liquors. Several recrystalli2ations from acetone yield an analytical sample, MP 262° to 265°C, [oIq is -2.1°. 

Three test batches of a chemical were manufactured with the intention of validating the process and having a new product to offer on the market. Samples were put on stability under the accepted ambient (25°C, 60% relative humidity) and accelerated (= stress 40°C, 75% rh) conditions cf. Section 4.20. One of the specification points related to the yellowish tinge imparted by a decomposition product, and an upper limit of 0.2 AU was imposed for the absorption of the mother liquor (the solvent mixture from which the crystalline product is precipitated) at a wavelength near 400 nm. 

The dichlorodibenzo-p-dioxin component was isolated by passing a dioxane solution of the mixture through acetate ion exchange resin to remove phenolics. The eluted product was recrystallized from benzene. The x-ray powder diffraction pattern of the precipitate was identical with that of 2,7-dichlorodibenzo-p-dioxin. Analysis of the mother liquor by GLC showed a singular peak consistent with 2,7-dichlorodibenzo-p-dioxin. The mother liquor was cooled to 5°C and yielded transparent crystals. This material had an x-ray diffraction pattern congruent to a sample of 2,8-dichlorodibenzo-p-dioxin obtained from A. E. Pohland (FDA). The two patterns were quite distinct from each other 14, 15). 

The mother liquor is evaporated to dryness on the water bath, and the powdered residue is extracted with alcohol in an extraction apparatus. Semicarbazone crystallises out in the flask of the apparatus. If a sample of the main portion of the material leaves a considerable amount of ash when ignited on platinum foil, this portion also should be extracted in the same way. 

The submitters recrystallized the sample from EtOAc-hexanes and obtained a yield of 93%. The checkers yield is based on combined product from two successive crops, although additional product weis observed in the remaining mother-liquor (2 g of cmde materieil) which could be used, as obtained, for subsequent reactions. The physical and spectroscopic properties of 3 are as follows mp 104-106°C (material isolated by column chromatography alone) mp 110-112°C [a]p°-24.6° (EtOAc, cl.O) (after a single crystallization from EtOAc/hexane) mp 119-121 C [a]Q°-24.1° (EtOAc, cO.8) (after two... 

The sample is placed in a controlled environment to define the temperature state of the sample with a cooling cell (Bartunik and Schubert, 1982, Helliwell, 1985), or the state of the mother liquor with a flow cell (Hajdu et al., 1985). Pressure cells... 

Later on we succeeded in partially aligning microcrystals within the sample they were placed in X-ray capillaries and pulled down by gently sucking their mother liquor, whereupon the needle-shaped crystals oriented along the capillary axis. Such samples sometimes, but only under perfect measuring conditions, produced pseudo fiber patterns which consisted of oriented arcs with average length of 60° (Fig. lb). In many cases these arcs were comj sed of distinct spots that could be clearly resolved by eye. Since such patterns may arise from partial orientation of the nucleic acid component within fairly well packed particles, these patterns indicated reasonable internal order. 

The VPI-5 samples prepared using TBA show greater thermal stability than those synthesized with DPA (ref. 3). Also, the TBA synthesized VPI-5 is stable in its mother liquor while the DPA synthesized VPI-5 is not (refs. 4, 5). The differences in stability are not due to pH variations between TBA and DPA mother liquors. Thus, the quaternary ion appears to assist the crystallization process in some manner that is not possible with an amine. Unfortunately, TBAOH is very expensive compared to most amines. 

Formerly all the iodine was made from the ash of seaweed, and potash was a remunerative appendix to the iodine industry but just as the Stassfurt salts killed those industries which extracted potash from other sources, so did the separation of iodine from the caliche mother-liquors threaten the industrial extraction of iodine from seaweed with extinction. Iodine in a very crude form was exported from Chili in 1874—e.g. a sample was reported with iodine 52-5 per cent. iodine chloride, 3-3 sodium iodate, 13 potassium and sodium nitrate and sulphate, 15 9 magnesium chloride, 0 4 insoluble matter, 1 5 water, 25-2 per cent. About that time much of the iodine was imported as cuprous iodide. This rendered necessary the purification of the Chilian product but now the iodine is purified in Chili before it is exported. The capacity of the Chilian nitre works for the extraction of iodine is greater than the world s demand. It is said that the existing Chilian factories could produce about 5100 tons of iodine per annum whereas the... 

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