1. In a 2000ml rotary glass evaporation reactor, add 1100ml of toluene solution and 160ml of methylamine aqueous solution. The water bath temperature is constant at 45°C. Start stirring, control the stirring speed to 65 rpm, and add α-bromopropiophenone dropwise. 210 g, then added dropwise 15% aqueous sodium hydroxide solution prepared by 50 g of sodium hydroxide, after the addition was complete, reacted for two hours, stopped heating, and cooled to room temperature. Use an extractor to separate the organic phase, extract the aqueous phase twice with toluene (300ml*2 times), and combine the organic phases. Add 1500 ml of 15% hydrochloric acid aqueous solution dropwise to the organic phase, stir for 1 hour, separate the aqueous phase, and evaporate under reduced pressure until it becomes syrupy. Add 550 ml of acetone and shake, let it stand overnight, and filter out the white solid, which is the hydrochloride of α-methylaminopropiophenone (yield: 74%).
2. In a 1000ml glass reactor, weigh and add 200g of α-methylaminopropiophenone hydrochloride, stir at 30 rpm, add 400ml of saturated sodium hydroxide to adjust to pH=12-13, stir and dissolve. Then add 100L of ethyl acetate, stir and let stand for layering. Discard the lower alkali aqueous solution to obtain 260ml of the upper layer of a mixed liquid of ethyl acetate and α-methylaminopropiophenone for later use. In addition, take 190g of the resolving agent (2R, 3S)-(-) dibenzoyl tartaric acid [(2R, 3S)-(-)DBT A.H2O] in the 1000ml reactor, add 100ml of ethyl acetate, dissolve, and slowly Add it to the "mixed liquid of ethyl acetate and α-methylaminopropiophenone". A large amount of precipitation will occur during the dripping process. After the dripping is completed, add 30ml of anhydrous methanol to clarify the solution. Do not stir, and leave it to allow natural crystallization for 24 seconds. hours or more. Centrifuge, and the mother liquor will be used for processing. The solid will be washed with a solution of ethyl acetate: methanol = 7:1 until the color of the product becomes colorless or dark red. The obtained solid is the salt of (2R, 3S)-(-)dibenzoyltartaric acid (S)-(-)-α-methylaminopropiophenone (abbreviation: Intermediate No. 1). Add 0.55 mol of the reducing agent potassium borohydride to 6 times the amount of pure water to reduce the weight of 216g, and then add hydrochloric acid to acidify. Extract with butyl acetate to separate and extract the resolving agent dibenzoyl tartaric acid. Add 40% sodium hydroxide to the acidic water layer to free it. Extract with toluene, and add hydrochloric acid to the extract for acidification and crystallization to prepare L-(-)ephedrine hydrochloride. The primary yield is 32.68%.
2. In a 1000ml glass reactor, weigh and add 200g of α-methylaminopropiophenone hydrochloride, stir at 30 rpm, add 400ml of saturated sodium hydroxide to adjust to pH=12-13, stir and dissolve. Then add 100L of ethyl acetate, stir and let stand for layering. Discard the lower alkali aqueous solution to obtain 260ml of the upper layer of a mixed liquid of ethyl acetate and α-methylaminopropiophenone for later use. In addition, take 190g of the resolving agent (2R, 3S)-(-) dibenzoyl tartaric acid [(2R, 3S)-(-)DBT A.H2O] in the 1000ml reactor, add 100ml of ethyl acetate, dissolve, and slowly Add it to the "mixed liquid of ethyl acetate and α-methylaminopropiophenone". A large amount of precipitation will occur during the dripping process. After the dripping is completed, add 30ml of anhydrous methanol to clarify the solution. Do not stir, and leave it to allow natural crystallization for 24 seconds. hours or more. Centrifuge, and the mother liquor will be used for processing. The solid will be washed with a solution of ethyl acetate: methanol = 7:1 until the color of the product becomes colorless or dark red. The obtained solid is the salt of (2R, 3S)-(-)dibenzoyltartaric acid (S)-(-)-α-methylaminopropiophenone (abbreviation: Intermediate No. 1). Add 0.55 mol of the reducing agent potassium borohydride to 6 times the amount of pure water to reduce the weight of 216g, and then add hydrochloric acid to acidify. Extract with butyl acetate to separate and extract the resolving agent dibenzoyl tartaric acid. Add 40% sodium hydroxide to the acidic water layer to free it. Extract with toluene, and add hydrochloric acid to the extract for acidification and crystallization to prepare L-(-)ephedrine hydrochloride. The primary yield is 32.68%.
,I read (Amino alcohol via Akabori) raction in web I want do this for phenyl propanol amine with alanine & benzaldehyde but l-alanine easy find in my region،Can phenylpropanol Amine made from this isomer(l-alanine) be converted into the active form of amphetamine(d)? or l-ephedrine with methyled PPA to eph?