Columns flash chromatography

Reaction of 5n,6,7,8,9,l l-hexahydropyrido[2,l-f ][l,3]benzothiazine-7,l 1-dione (47, X = S, R = H) and 2-amino-6-fluorobenzamidine dihydrochloride in boiling EtOH yielded a diastereomeric mixture of spiro derivatives 48 (X = S, R = H), which were separated by flash column chromatography (OOMIPl). 

Flash column chromatography was performed using silica gel (6 cm diameter x 35 cm height), eluting with 19/1 hexane/diethyl ether. 

Flash column chromatography was performed using silica gel (10 cm diameter 27 cm height), eluting with 4/1 toluene/hexane. A small amount of aryl chloride that remained unreacted after 72 hr was recovered mixed with a small quantity (<5%) of the desired product. 

In order to reduce the time-consuming open-column chromatographic processes, conventional methods of hydrocarbon-group-type separation have been replaced by MPLC and HPLC. Flash column chromatography is a technique less commonly applied than open-column version, but several applications have been described [2,24—27]. The common technique version is to use a silica-gel-filled column for example, 230 to 400 mesh 20 X 1 cm column size with a back pressure of 1.5 X 10 Pa of an ambient gas such as nitrogen. Solvents are similar to the ones apphed in the case of open-column chromatography fractionations. 

Ethoxy-l,3,2-oxazaphospholidine 59 was prepared as a single diastereomer from (-)ephedrine (42) and ethyl dichlorophosphite 57. Its Arbusov reaction with allyl bromide gave the corresponding allyl phosphonates 61a,b as a diastereomeric mixture which could be separated by flash column chromatography and crystallization (Scheme 21) [48], On applying a similar protocol, starting from... 

Flash column chromatography was performed using Merck 60-silica gel (40-63 pm) and solvents were obtained commercially and used as received. 

Purification by flash column chromatography on silica (eluent petroleum ether-ethyl acetate, 2 1) gave a crystalline solid (S)-TV-(tert-butoxycarbonyl)-l-(4-methoxyphenyl)-2-hydroxyethylamine (296 mg, 74%). 

The crude reaction mixture was purified by flash column chromatography (10% ethyl acetate in hexane) to give the product as a colourless liquid (0.9 g, 90% yield). 

The reaction was performed in flame-dried modified Schlenk (Kjeldahl shape) flask fitted with a glass stopper or rubber septum under a positive pressure of argon. Trifluoromethanesulfonic anhydride (1.4 equiv) was added to a solution of giycosyl donor (0.191 mmol, 1 equiv) and diphenyl sulfoxide (2.8 equiv) in a mixture of toluene and dichloromethane (8 ml, 3 1 vol/vol) at — 78 °C. The reaction mixture was stirred at this temperature for 5 min and then at —40 °C for 1 h. At this time, 2-chloropyridine (5.0 equiv) and the giycosyl acceptor (3.0 equiv) were added sequentially at —40 °C. The solution was stirred at this temperature for 1 h, then at 0 °C for 30 min and finally at 23 °C for lh before the addition of excess triethylamine (10 equiv). The reaction was diluted with dichloromethane (100 ml) and was washed sequentially with saturated aqueous sodium bicarbonate solution (2 x 100 ml) and saturated aqueous sodium chloride (100 ml). The organic layer was dried (sodium sulfate) and concentrated. The residue was purified by silica gel flash column chromatography. 

General procedure for the preparation of 4-functionalized-l-alkyl-3-methylindoles (2) A solution of the starting amine 1 (2 mmol) in THF (15 mL) was treated with /BuLi (7 mmol, 3.5 equiv) at -110°C. The reaction mixture was stirred at this temperature for 15 min and then at -40°C for 3 h. The reaction mixture was re-cooled to -78°C and the electrophile (3 mmol) was added. The reaction mixture was stirred overnight at room temperature, then hydrolyzed with water, and extracted with ethyl acetate (3 x 20 mL). The combined organic layers were dried over anhydrous Na2S04. The solvent was removed under vacuum and the residue was purified by flash column chromatography (hexane/ethyl acetate) and/or by recrystallization to afford products 2. 

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