2.2- Dimethoxypropane, extraction

Female guinea pigs are immunised by injection of 200 pg of 3/ -hydroxy-5-chole-noyl-thyroglobulin conjugate. Serum extraction, solvolysis and alkaline hydrolysis of BAs are performed according to the method of Ali and Javitt [46] 3.5 ml of 2,2-dimethoxypropane and 0.4 ml of 1 M hydrochloric acid in methanol are added to... 

The reaction is cooled to room temperature and approximately 50 mL of toluene and 35 mL of 5% sodium carbonate solution are added. The organic layer is separated, extracted with 3 x 50 mL of 5% sodium carbonate solution, dried over MgS04, and filtered. The toluene is removed on a rotary evaporator and the residue dissolved in 20 mL of methylene chloride. The concentrated solution is absorbed at the top of a column of alumina (2 x 20 cm ca. 100 g of activity III) and eluted with 150 mL of CH2C12 to remove any unreacted pyrazole. The solvent is removed on a rotary evaporator and the solid is recrystallized from 100 mL hexanes to give 10.28 g of the product as white crystals melting at 84-86°C. A second crop of product (0.60 g) can be obtained by concentration of the filtrate, giving an overall yield of 10.88 g (62%) based on 2,2-dimethoxypropane. 

Neutral phosphates (RO)sPO, phosphonates (RO)2R PO and phosphinates (RO)R2PO are well known as extracting agents for metal ions.1823 The isolation of their metal complexes as crystalline compounds is, in general, more difficult than the preparation of complexes with other substituted phosphoryl compounds. It is often essential to reflux solutions of the reactants with dehydrating agents such as triethyl orthoformate or 2,2 -dimethoxypropane. In some cases the neutral phosphoryl ligands or triethyl orthoformate by themselves act as the reaction media in the synthesis of the nickel(II) complexes. 

An unsuccessful attempt was next made to simplify the problem of purifying the product by using dioxane as the extracting solvent with only enough benzaldehyde for solvolysis. Finally, on the assumption that an acetal should be as effective in transacetalization as an aldehyde or ketone, the benzaldehyde was replaced by 2,2-dimethoxypropane. In several experiments the hydrogen chloride was replaced by -toluenesulfonic acid also, dimethyl sulfoxide was tried instead of dioxane. All these experiments are summarized in Table I, and they lead to the following conclusions ... 

In this work we have, in a preliminary way, extracted periodate lignin by the continuous dioxane-dimethoxypropane-HCl procedure and obtained only about 11% of a soluble material which had the same infrared spectral characteristics as the lignin isolated from wood. The gel-like residue showed evidence of having undergone the same reaction but remained insoluble. This seemed to indicate that the reaction alone was not enough to confer solubility. 

By analogy to Pew s grinding procedure we considered the possibility that lignin was being released because the cellulose was hydrolyzed, and we examined this point by determining the effect of the reaction on the viscosity of cellulose. When we extracted pure cotton cellulose with dioxane-dimethoxypropane-HCl for 3 hours, we found that viscosity decreased greatly. 

Acetals such as dimethoxypropane and diethoxypropane with hydrogen chloride in dioxane extract lignin from wood much more rapidly than methanol, acetone, or water. When the extraction is performed in a Soxhlet extractor, unusually high yields of lignin are obtained. 

Extracts of a mixture of honiokol 202 and magnolol 203 (the main constituents of the stem bark of Magnolia abovata thumb and Magnolia officinalis rhed, used in traditional Chinese medicine) have been separated by acid-catalyzed transformation of magnolol with dimethoxypropane into 204 (Scheme 57) <2006JME3426>. 

Camphorsulphonic acid monohydrate (catalytic amount) was added to a stirred solution of [lR-[la,2a,3 3,4a(R),5a,6a)-3-benzyloxy-5,6-epoxy-4-(l-phenylethoxy)cyclohexane-l,2-diol (0.321 g, 0.9 mmol) in 2,2-dimethoxypropane (10 ml) at RT under argon. After 16 h, the mixture was poured into DCM and washed with aqueous sodium bicarbonate solution and water. The aqueous layers were reextracted with DCM and the combined organic extracts dried (MgS04) and evaporated in vacuum column chromatography (50% ether-petrol) of the residue afforded the title epoxy acetonide (0.317 g, 89%) as needles, m.p. 114°-115°C (recrystallized from ether-petrol) [a]D2°+134.1° (c 1.00, CHCI3). 

B. 3-(1,1-Dimethylethyl) 4-methyl-(S)-2,2-dimethyloxazolidine-3,4-dicarbox-ylate (3). To a solution of N-Boc-L-serine methyl ester (10.0 g, 45.6 mmol) in acetone (165 mL) is added 2,2-dimethoxypropane (50 mL, 400 mmol) and boron trifluoride etherate (BF3-OEt2, 0.35 mL, 2.8 mmol) (Notes 9 and 10). The resulting orange solution is stirred at room temperature for 2.5 hr when TLC analysis indicates the reaction to be complete (Note 11). The reaction mixture is treated with 0.9 mL of 99% triethylamine and the solvent is removed under reduced pressure. The residual brown syrup Is partitioned between diethyl ether (150 mL) and saturated aqueous sodium bicarbonate solution (250 mL). The aqueous layer is extracted with diethyl ether (2 x 150 mL) and the combined organic phases are dried with anhydrous sodium sulfate and concentrated under reduced pressure (7 mm and 65°C bath temperature) to give 10.4-10.8 g (88-91% crude yield) of oxazolidine methyl ester 3 as a pale yellow oil (Note 12). Analysis of crude 3 by 1H NMR indicates a chemical purity of > 95%. The product can be used without further purification. 

Lads 2 OMPA H2O. Hydrated lanthanum chloride (0.0031 mole) was dissolved in a mixture of 2 ml. of 2,2-dimethoxypropane and 4 ml. oiF methanol. The solution was stirred for 1 hours at room temperature, and 0.0124 moles of OMPA was added. When ether was added, an oil separated from solution, which was extracted several times until a white precipitate formed. 

To a stirred solution of the diol starting material (0.8 g, 2.85 mmol) in CHiCL (2 mL) at room temperature was added 2,2,-dimethoxypropane (0.52 mL, 4.2 mmol) and camphorsulfonic acid (CSA, 13 mg, 2 mol%). The reaction was stirred for 3 h and quenched with saturated aqueous sodium bicarbonate (10 mL) and the aqueous layer was extracted with ether (3 x 15 mL). The combined organic layers were washed with brine (10 mL), dried (Na2SO4), filtered, and concentrated in vacuo. Purification of the residue by flash chromatography eluting with EtOAc/hexane (1 9) afforded the isopropylidene acetal (0.73 g, 80%) as a viscous oil. 

A solution of this ester (8.35 g, 21.6 mmol, 1.0 equivalents) in tetrahydrofuran (THF 100 mL) was cooled to 0 °C, and pyridinium p-toluenesulfonate (PPTS, 500 mg, 2.00 mmol, 0.1 equivalents) and then 2,2-dimethoxypropane (20.0 mL, 163 mmol, 5.9 equivalents) were added. The cold bath was removed and the mixture was stirred at room temperature for 48 h, quenched with saturated aqueous NaHCOs solution, and extracted with EtOAc. The combined organic layers were washed with brine, dried (Na2SO4), filtered, and concentrated. Purification by chromatography on SiO2 (3% ethyl acetate and 1% triethylamine in hexanes, and then 100% EtOAc) afforded the acetonide and a small amount of starting diol which was re-subjected and purified as above. The two batches were combined to afford naphthalene-2-carboxylic acid 2-[(4S)-2,2- dimethyl-[l,3]dioxan-4-yl]-2-methylpropyl ester (9.140 g, 97%) as a clear colorless syrup. Reference Wipf, P Graham, T. H.,/. Am. Chem. Soc. 2004,126, 15346-15347. 

The crude residue in a 30-mL round-bottomed flask was treated with p-toluenesulfonic acid monohydrate (30 mg) in dry dimethyl formamide/2,2-dimethoxypropane (4.5 mL/4.5 mL) at room temperature for 2 hours (TLC hexane/acetone = 2/1, acetal derived from ketone Rf = 0.82, vy -acetonide Rf = 0.76, awfi-acetonide Rf 0.56). Saturated aqueous sodium hydrogen carbonate (12 mL), water and ether were added to the mixture and the aqueous layer was separated and extracted with diethyl ether (x 2). The combined organic layers were washed with water and with brine (x 2) and dried over sodium sulfate. The solvent was removed under reduced pressure and the resulting residue was analysed to determine the diastereomeric ratio of the aldol products by 1H NMR (in CDCI3, H at C-2, vyn-acetonide 5 4.95, awfi-acetonide 8 5.48). The crude residue was purified by flash silica gel column chromatography (hexane/ether/acetone 30/1/1) to afford the acetonides. The diastereomers were separated by this procedure. The enantiomeric excesses of the acetonides were determined by HPLC after cleavage of the acetonides (DAICEL CHIRALCEL OD, 2-propanol/hexane 20/80, flow l.OmL/min, detection at 254 nm, tR 13.6 min (minor(25,3/ )) and 15.9 min (major(2/ ,3S)). The results obtained from various aldehydes are summarized in Table 11.1. 

Under the protection of nitrogen, the substrate 2.2.13 (320 mg, 1.36 mmol) and 2,2-dimethoxypropane (0.34 mL, 2.72 mmol) were added to acetone (10 mL), which was cooled to 0 °C. Monohydrate p-toluenesulfonic acid (26 mg, 0.136 mmol) was added, and the reaction was stirred at room temperature for 0.5 h. TLC showed that the reaction was completed. The reaction was cooled to 0 °C. Then, saturated NaHCOs (5 mL) was added dropwise. The acetone solvent was removed by vacuum rotary evaporator, and ethyl acetate (50 mL) was added. The aqueous phase was extracted with ethyl acetate (3 x 50 mL). The organic phases were combined, washed with saturated brine (20 mL), dried over anhydrous sodium sulfate, and hltered. The hltrate was concentrated by rotary evaporator under reduced pressure, and the resulting crude product was separated and purihed by flash column chromatography (PE/EA = 10 1). 300 mg desired product was obtained as a white solid (Rf — 0.80, PE/EA = 5 1), yield 92 (%). 

With the removal of the mobile phase, IR detection no longer restricts the selectivity of the chromatographic process through solvent-transparency requirements. Solvent elimination is more difficult with reversed-phase chromatography because of the presence of water. This problem can be overcome by extraction with organic solvent, and deposition of the organic solution in a known manner, or by a post-colunrn reaction with 2,2-dimethoxypropane, converting water into methanol and acetone, which have sufficient volatility for the deposition technique. 

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