Background and overview[1]
(Methoxymethyl)triphenylphosphorus chloride, (p-tolyloxymethyl)triphenylphosphorus chloride and (2-tetrahydrofuranoxymethyl)triphenylphosphorus chloride are An important reagent in organic synthesis, it is treated with a strong base and then reacted with various aldehydes or ketones for Wittig reaction. The resulting alkoxy or aryloxy olefin is hydrolyzed to form an aldehyde with one more carbon atom than the original aldehyde or ketone. Compared with other methods, this method has the advantages of short steps, mild reaction conditions, and simple operation. Among such reagents, (methoxymethyl)triphenylphosphorus chloride has a simple structure, the subsequent reaction is easy to control with antioxidants, and the product is easy to purify.
Preparation[1]
A synthesis method of (methoxymethyl)triphenylphosphonium chloride, including the following steps:
Under nitrogen protection, add 50 mL anhydrous acetone to the reactor, then add 32 g triphenylphosphine, raise the temperature to 37°C while stirring, maintain a constant temperature, and add 20 g methyl chloromethyl ether into the reactor , then reacted at 37°C for 3h, slowly raised the temperature to 47°C at a rate of 1°C/min, continued the reaction for 3h, stopped the reaction, filtered, washed with anhydrous ether, and dried to obtain 37.0g (methoxymethyl ) triphenylphosphonium chloride, the yield was 88.5%.
Apply[2-3]
CN201811357899.7 reports a synthesis method of 2-cyclopropylpropionaldehyde, which reacts (methoxymethyl)triphenylphosphorus chloride with cyclopropylmethylketone under the action of alkali to generate 1 -Methoxy-2-cyclopropylpropionaldehyde; 1-methoxy-2-cyclopropylpropionaldehyde is then acidified and hydrolyzed to generate 2-cyclopropylpropionaldehyde. The 2-cyclopropylpropanal synthesized by the invention has a yield of more than 95% calculated based on cyclopropyl methyl ketone, and has the advantages of less by-products, high yield and low cost.
CN201910830617.9 discloses a synthesis method of (4S)-N-Boc-4-methoxymethyl-L-proline, which includes using L-hydroxyproline as a starting material. The steps of protecting Boc to obtain N-Boc-L-hydroxyproline; oxidizing N-Boc-L-hydroxyproline-soluble silicone oil emulsion in a solvent with TEMPO (tetramethylpiperidine nitrogen oxide) to obtain (2S )-N-Boc-4-oxopyrrolidine-2-carboxylic acid; combine (2S)-N-Boc-4-oxopyrrolidine-2-carboxylic acid and (methoxymethyl)triphenyl The step of preparing (2S)-N-Boc-4-methoxymethylenepyrrolidine-2-carboxylic acid by dissolving phosphorus chloride in a solvent and performing a wittig reaction; (2S)-N-Boc-4-methyl Oxymethylpyrrolidine-2-carboxylic acid and tert-butylamine are dissolved in water and subjected to hydrogenation reaction to prepare (4S)-N-Boc-4-methoxymethyl-L-proline; this reaction shortens the reaction steps ; Avoiding the use of highly toxic cyanide, increasing safety and reducing environmental pressure; improving atomic economy and reducing waste emissions; and the cost of raw materials has dropped significantly.
