2-(Methylamino)-1-phenylpropan-1-ol (Eph) to N-Methyl-1-phenylpropan-2-amine (Meth)

Query Query

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Date

14 reactions in Reaxys

2017-11-28 21h:22m:20s (EST)

HO

1. Query

HN

Search as: As drawn, No salts, No mixtures

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H N

H

OH

HN

H

Rx-ID: 356231 View in Reaxys 1/14 Yield

Conditions & References

100 %

1 : Example 1 General Procedure for the Reaction of the Excipient of Formulas I and II and Pseudoephedrine with Lithium in Liquid Ammonia General procedure: Example 1 General Procedure for the Reaction of the Excipient of Formulas I and II and Pseudoephedrine with Lithium in Liquid Ammonia (0044) Lithium metal pieces (35 mg, 5.0 mmol) were carefully added to liquid ammonia (5-10 mL) at about −78° C. (dry ice, isopropyl alcohol). A dark blue solution began to form within a few seconds. The dark blue solution was stirred at −78° C. for about 3 to 5 minutes. Thereafter, a mixture of the excipient of Formula I (122-166 mg, 1.0 mmol) and pseudoephedrine (165 mg, 1.0 mmol) in anhydrous tetrahydrofuran (3 mL) was added to the dark blue solution. The entire reaction mixture was stirred while the temperature of the reaction was slowly raised to about −20° C. Stirring was continued at this temperature for about 1 hour. The reaction mixture was quenched with saturated ammonium chloride (2 mL) and water (3 mL), and diluted with methanol (5 mL). The reaction mixture was analyzed and quantified for the presence of methamphetamine. The results are given in Example 3 below. With ammonia, lithium in tetrahydrofuran, Time= 1h, T= -78 - -20 °C , Reagent/catalyst Patent; Satara Pharmaceuticals, LLC; Rajagopalan, Raghavan; (9 pag.); US2016/89439; (2016); (A1) English View in Reaxys

<1%

1 :Example 1. General Procedure for the reaction of the exipient of Formulas I and II and pseudoephedrine with lithium in liquid ammonia. Lithium metal pieces (35 mg, 5.0 mmol) were carefully added to liquid ammonia (5-10 mL) at about -78 °C (dry ice, isopropyl alcohol). A dark blue solution began to form within a few seconds. The dark blue solution was stirred at -78 °C for about 3 to 5 minutes. Thereafter, a mixture of the exipient of Formula I (122-166 mg, 1.0 mmol) and pseudoephedrine (165 mg, 1 .0 mmol) in anhydrous tetrahydrofuran (3 mL) was added to the dark blue solution. The entire reaction mixture was stirred while the temperature of the reaction was slowly raised to about - 20 °C. Stirring was continued at this temperature for about 1 hour. The reaction mixture was quenched with saturated ammonium chloride (2 mL) and water (3 mL), and diluted with methanol (5 mL). The reaction mixture was analyzed and quantified for the presence of methamphetamine. The results are given in Example 3 below. With acetylpyrazine, ammonia, lithium in tetrahydrofuran, Time= 1h, T= -78 - -20 °C , Reagent/catalyst, Temperature, Time Patent; DAYA DRUG DISCOVERIES, INC.; RAJAGOPALAN, Raghavan; WO2015/48597; (2015); (A1) English View in Reaxys With phosphorus, hydrogen iodide Ogata; zit. bei Emde; Helvetica Chimica Acta; vol. 12; (1929); p. 373 View in Reaxys

H N

H

OH

H

H N H

Cl

H

Rx-ID: 25930802 View in Reaxys 2/14 Yield 50 %

Conditions & References With ammonia, lithium in tetrahydrofuran, Time= 0.0833333h, T= -78 °C Matsumoto, Teruki; Urano, Yasuteru; Makino, Yukiko; Kikura-Hanajiri, Ruri; Kawahara, Nobuo; Goda, Yukihiro; Nagano, Tetsuo; Analytical Chemistry; vol. 80; nb. 4; (2008); p. 1176 - 1181 View in Reaxys Reaction Steps: 2 1: hydrochlorid acid / methanol / 0.5 h / 760.05 Torr

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2: palladium 10 on activated carbon; hydrogen / methanol / 16 h / 20 °C With hydrochlorid acid, palladium 10 on activated carbon, hydrogen in methanol Lalwani, Komal G.; Sudalai, Arumugam; Tetrahedron Letters; vol. 56; nb. 46; (2015); p. 6488 - 6490 View in Reaxys

H N

OH

H

H N Cl

H

Cl

H

Rx-ID: 25930804 View in Reaxys 3/14 Yield

Conditions & References

77 %

(S)-N-methyl-1-phenylpropan-2-amine hydrochloride (4): To a solution of ephedrine hydrochloride 1 (0.10 g, 6.2mmol) in methanolic HCl (10 mL) wasadded 10percent Pd/C (20 mg). The resulting solution was stirred under hydrogen (1 atmosphere) at 60 psi for 16 h at room temperature until disappearance of the starting compound as monitored by thin-layer chromatography (TLC). The reaction mixture was filtered through a celite pad to remove the catalyst, and the filtrate was concentrated in vacuo to get (S)metamphetamine hydrochloride 4 as colorless solid (64 mg). With palladium 10 on activated carbon, hydrogen in methanol, Time= 16h, T= 20 °C , enantioselective reaction Lalwani, Komal G.; Sudalai, Arumugam; Tetrahedron Letters; vol. 56; nb. 46; (2015); p. 6488 - 6490 View in Reaxys

65 %

With hydrochlorid acid, phosphorus, Time= 4.5h, T= 140 °C Matsumoto, Teruki; Urano, Yasuteru; Makino, Yukiko; Kikura-Hanajiri, Ruri; Kawahara, Nobuo; Goda, Yukihiro; Nagano, Tetsuo; Analytical Chemistry; vol. 80; nb. 4; (2008); p. 1176 - 1181 View in Reaxys

H N

Cl H HN

OH

H

Cl

H

Rx-ID: 25930803 View in Reaxys 4/14 Yield 80 %

Conditions & References Stage 1: With iodine, hypophosphorous acid, Heating Stage 2: With sodium hydroxide in water, pH= > 10 Stage 3: With hydrogenchloride in toluene David, Gabrielle E.; Hibbert, D. Brynn; Frew, Russell D.; Hayman, Alan R.; Australian Journal of Chemistry; vol. 63; nb. 1; (2010); p. 22 - 29 View in Reaxys

65 %

With phosphorus, hydrogen iodide, Time= 4.5h, T= 140 °C Matsumoto, Teruki; Urano, Yasuteru; Makino, Yukiko; Kikura-Hanajiri, Ruri; Kawahara, Nobuo; Goda, Yukihiro; Nagano, Tetsuo; Analytical Chemistry; vol. 80; nb. 4; (2008); p. 1176 - 1181 View in Reaxys Reaction Steps: 3 1: sodium hydrogencarbonate / water / 12 h / 20 °C 2: Raney Ni / isopropyl alcohol / 50 - 55 °C / |Autoclave 3: hydrogenchloride / ethyl acetate / 20 h / 0 - 20 °C / |Large scale With hydrogenchloride, sodium hydrogencarbonate in water, ethyl acetate, isopropyl alcohol Pramanik, Chinmoy; Bapat, Kiran; Chaudhari, Ashok; Kulkarni, Mukund G.; Kolla, Rangarao; Sompalli, Srinivasarao; Tripathy, Narendra K.; Gurjar, Mukund K.; Organic Process Research and Development; vol. 18; nb. 4; (2014); p. 495 - 500

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View in Reaxys OH

H N

H N Cl

H

Cl

H

Rx-ID: 29344283 View in Reaxys 5/14 Yield

Conditions & References Stage 1: With iodine, hypophosphorous acid, Heating Stage 2: With sodium hydroxide in water, pH= > 10 Stage 3: With hydrogenchloride in toluene David, Gabrielle E.; Hibbert, D. Brynn; Frew, Russell D.; Hayman, Alan R.; Australian Journal of Chemistry; vol. 63; nb. 1; (2010); p. 22 - 29 View in Reaxys

2H

Cl H

OH

HN

HCl

H

HN

H

Rx-ID: 29344284 View in Reaxys 6/14 Yield

Conditions & References Stage 1: With phosphorus, water-d2, Heating Stage 2: With sodium hydroxide in water, pH= > 10 Stage 3: With hydrogenchloride in toluene David, Gabrielle E.; Hibbert, D. Brynn; Frew, Russell D.; Hayman, Alan R.; Australian Journal of Chemistry; vol. 63; nb. 1; (2010); p. 22 - 29 View in Reaxys

H N

H

OH

H N Cl

H

Rx-ID: 588054 View in Reaxys 7/14 Yield

Conditions & References With sulfuric acid, palladium, acetic acid, T= 80 °C , Hydrogenation Rosenmund; Karg; Chemische Berichte; vol. 75; (1942); p. 1850,1856 View in Reaxys Kindler; Hedemann; Schaerfe; Justus Liebigs Annalen der Chemie; vol. 560; (1948); p. 215,219 View in Reaxys With perchloric acid, palladium, acetic acid, T= 60 °C , Hydrogenation Rosenmund; Karg; Chemische Berichte; vol. 75; (1942); p. 1850,1856 View in Reaxys Kindler; Hedemann; Schaerfe; Justus Liebigs Annalen der Chemie; vol. 560; (1948); p. 215,219 View in Reaxys With thionyl chloride, palladium on barium sulfate, hydrogen, sodium acetate, 1.) CHCl3, reflux, 3 h, 2.) AcOH, Yield given. Multistep reaction Noggle, F. Taylor; DeRuiter, Jack; Clark, C. Randall; Analytical Chemistry; vol. 58; nb. 8; (1986); p. 1643 - 1648 View in Reaxys Reaction Steps: 2 1: thionyl chloride / CHCl3

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2: H2 / Pd/C / ethanol With thionyl chloride, hydrogen, palladium on activated charcoal in ethanol, chloroform Armellin, Silvia; Brenna, Elisabetta; Frigoli, Samuele; Fronza, Giovanni; Fuganti, Claudio; Mussida, Daniele; Analytical Chemistry; vol. 78; nb. 9; (2006); p. 3113 - 3117 View in Reaxys

H N

H

OH

H N H

H

Rx-ID: 333846 View in Reaxys 8/14 Yield

Conditions & References With phosphorus, hydrogen iodide Ogata; zit. bei Emde; Helvetica Chimica Acta; vol. 12; (1929); p. 373 View in Reaxys 1 :In a controlled laboratory setting, 12 microliters of the commercial product marketed AS"KEYACIDTM Rhodamine WT"and manufactured by Keystone Analine Corporation of Chicago, Illinois, which is a 21.2percent w/w solution of rhodamine WT in water, and 300 ML of anhydrous ammonia were combined in a flask. This is approximately equivalent to 2 oz OF KEYACID Rhodamine WT in one ton of liquid anhydrous ammonia. The mixture was stirred until a solution formed that had a very slight yellow tint. The solvation of rhodamine WT in ammonia transformed the rhodamine WT into a nearly colorless composition. The surface of each piece of equipment used in this process, however, was visibly stained a light pink in areas exposed to the ammonia and from which the ammonia had evaporated. The solution was also purposefully put in contact with various additional equipment and materials, including metal screwdriver heads, concrete, and paper. All exposed equipment and materials were visibly stained pink upon evaporation of the anhydrous ammonia. During the mixing process, some of the mixture unintentionally contacted items, including protective gloves and the hands of the researchers who were performing the mixing. These additional items were also visibly stained pink. [0071] The solution of dye in ammonia was added to 2 grams of pure pharmaceutical grade ephedrine in a 500 mL beaker. The contents of the flask were stirred to dissolve the ephedrine. Any material that came into contact with this solution, including the flask when the flask was emptied, was also visibly stained pink upon evaporation of the ammonia solvent. The visible pink stain on the flask was transferred to a sponge when the flask was washed. [0072] Lithium metal was added to the ephedrine solution. This mixture was heated to carry out a so-called"Birch"reaction. During the Birch reaction, materials contacted by the mixture were not stained. It is believed that the lack of a stain at this stage may be due to a reduction of the rhodamine WT to a colorless composition. [0073] Evaporation of the ammonia from the Birch reaction mixture left a free base form of methamphetamine. In order to purify it, the free base methamphetamine was dissolved into a liquid ether and converted to the hydrochloride salt by bubbling hydrogen chloride gas through the solution. The methamphetamine salt precipitated from solution. During this process plastic tubes used to carry the hydrogen chloride gas into the dissolved methamphetamine were visibly stained pink as was the beaker. [0074] The methamphetamine salt product was filtered through a coffee filter to retain the methamphetamine. The coffee filter used for this filtration along with the resultant product is shown in the picture of FIG. 3. Two things were observed. First, the coffee filter and resulting product are both stained pink. Further, the filtration does not occur easily because instead of a rapidly-drying, clear crystal being formed, the product was a pink sludge, which was difficult to filter and dry. This pink sludge (methamphetamine) visibly stained objects with which it came into contact pink, including plastic storage bags. With ammonia, lithium in water, Birch Reduction Patent; GLOTELL PRODUCTS, INC.; BICKETT, Tim; EITER, Frank; WO2005/32458; (2005); (A2) English View in Reaxys

H N

OH

H N

Rx-ID: 12886381 View in Reaxys 9/14 Yield

Conditions & References Reaction Steps: 2 1: SOCl2

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2: H2 / Pd/BaSO4 With thionyl chloride, hydrogen, Pd-BaSO4 Kurashima, Naoki; Makino, Yukiko; Sekita, Setsuko; Urano, Yasuteru; Nagano, Tetsuo; Analytical Chemistry; vol. 76; nb. 14; (2004); p. 4233 - 4236 View in Reaxys

H N

Cl H

OH

HN

H

Rx-ID: 4260641 View in Reaxys 10/14 Yield

Conditions & References With thionyl chloride, palladium on barium sulfate, hydrogen, sodium acetate, 1.) CHCl3, reflux, 3 h, 2.) AcOH, Yield given. Multistep reaction Noggle, F. Taylor; DeRuiter, Jack; Clark, C. Randall; Analytical Chemistry; vol. 58; nb. 8; (1986); p. 1643 - 1648 View in Reaxys

OH

H N

Cl

H H

Rx-ID: 4271306 View in Reaxys 11/14 Yield

Conditions & References With thionyl chloride, palladium on barium sulfate, hydrogen, sodium acetate, 1.) CHCl3, reflux, 3 h, 2.) AcOH, Yield given. Multistep reaction Noggle, F. Taylor; DeRuiter, Jack; Clark, C. Randall; Analytical Chemistry; vol. 58; nb. 8; (1986); p. 1643 - 1648 View in Reaxys

H N

OH

H

H N Cl

H

Rx-ID: 4271308 View in Reaxys 12/14 Yield

Conditions & References With thionyl chloride, palladium on barium sulfate, hydrogen, sodium acetate, 1.) CHCl3, reflux, 3 h, 2.) AcOH, Yield given. Multistep reaction Noggle, F. Taylor; DeRuiter, Jack; Clark, C. Randall; Analytical Chemistry; vol. 58; nb. 8; (1986); p. 1643 - 1648 View in Reaxys

H N

OH

H

H N H

Rx-ID: 2104711 View in Reaxys 13/14 Yield

Conditions & References With hydrogenchloride, hydrogen, phosphorus pentabromide, palladium on activated charcoal, Yield given. Multistep reaction Buckley, Thomas F.; Rapoport, Henry; Journal of the American Chemical Society; vol. 103; nb. 20; (1981); p. 6157 - 6163

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View in Reaxys

H N

Cl H

OH

H

NH

H

racemate

Rx-ID: 588058 View in Reaxys 14/14 Yield

Conditions & References With perchloric acid, palladium, acetic acid, T= 80 °C , Hydrogenation Rosenmund; Karg; Chemische Berichte; vol. 75; (1942); p. 1850,1856 View in Reaxys

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