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12 reactions in Reaxys
2018-06-23 11h:33m:46s (UTC)
H 2N
1. Query
Search as: Product, As drawn, No mixtures ) AND (RX.PRO='phentermine hydrochloride'))
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H 2N
O
Cl
H
HO
Rx-ID: 29555741 View in Reaxys 1/12 Yield
Conditions & References 75 :Intermediate 75; 2-Methyl-1 -phenyl-2-propanamine; DPPA (16.87 g, 61.31 mmol) was added with external cooling to a stirred solution of 2,2- dimethyl-3-phenylpropanoic acid (10.21 g, 57.30 mmol) and triethylamine (6.20 g, 61.3 mmol) in dry toluene (100 ml_). A slightly exothermic reaction commenced and was completed after about 1 hour. The reaction mixture was stirred for an additional 1 hour at room temperature, followed by refluxing for 3 hours. The solution was cooled and washed with water (3 X 100 ml_), and the toluene phase was separated, dried over Na2SO4, and evaporated in vacuum. A mixture of 15percent hydrochloric acid (20 ml.) and acetic acid (20 ml.) was added, and the resulting mixture was stirred at room temperature overnight. The mixture was partitioned between EtOAc and water. The aqueous layer was extracted with EtOAc (4 X 50 ml_), and the aqueous was concentrated in vacuum to afford the HCI salt of the title compound (5.21 g) as a white solid. LC-MS (ES) m/z = 150 [M+H]+. Stage 1: With diphenyl phosphoryl azide, triethylamine in toluene, Time= 5h, Reflux, Cooling Stage 2: With hydrogenchloride, acetic acid in water, T= 20 °C Patent; GLAXOSMITHKLINE LLC; AXTEN, Jeffrey, Michael; BLACKLEDGE, Charles, William; BRADY, Gerald, Patrick; FENG, Yanhoug, G.; GRANT, Seth, W.; MEDINA, Jesus, Rahul; MILLER, William, H.; ROMERIL, Stuart, P.; WO2010/59658; (2010); (A1) English View in Reaxys DPPA (16.87 g, 61.31 mmol) was added with external cooling to a stirred solution of 2,2- dimethyl-3-phenylpropanoic acid (10.21 g, 57.30 mmol) and triethylamine (6.20 g, 61.3 mmol) in dry toluene (100 ml_). A slightly exothermic reaction commenced and was completed after about 1 hour. The reaction mixture was stirred for an additional 1 hour at room temperature, followed by refluxing for 3 hours. The solution was cooled and washed with water (3 X 100 ml_), and the toluene phase was separated, dried over Na2SO4, and evaporated in vacuum. A mixture of 15percent hydrochloric acid (20 ml.) and acetic acid (20 ml.) was added, and the resulting mixture was stirred at room temperature overnight. The mixture was partitioned between EtOAc and water. The aqueous layer was extracted withEtOAc (4 X 50 ml_), and the aqueous was concentrated in vacuum to afford the HCI salt of the title compound (5.21 g) as a white solid. LC-MS (ES) m/z = 150 [M+H]+. Stage 1: With diphenylphosphoranyl azide, triethylamine in toluene, T= 20 °C , Reflux Stage 2: With hydrogenchloride, water, acetic acid, T= 20 °C Patent; GLAXOSMITHKLINE LLC; AXTEN, Jeffrey, Michael; BRADY, Gerald, Patrick, Jr.; GALLAGHER, Timothy, Francis; HEERDING, Dirk, A.; MEDINA, Jesus, Raul; ROMERIL, Stuart, Paul; WO2010/120854; (2010); (A1) English View in Reaxys
H 2N
H 2N Cl
H
Rx-ID: 23770584 View in Reaxys 2/12 Yield
Conditions & References 5.D :A mixture of the chloroacetamide from Step C above (12.2 g, 54.2 mmol), thiourea (2.7 g, 65 mmol) and acetic acid (10.6 mL, 0.325 mol) in absolute ethanol (60 mL) was heated to reflux to 16 h. The reaction mixture was then diluted with water (50 mL) and extracted with EtOAc (2*75 mL). The combined organic fractions were washed with brine (5*50 mL), dried over MgSO4 and evaporated in vacuo. Distillation under high vacuum provided the free amine (bp 125° C.at;6 Torr). This crude material was dissolved in Et&2O
and 4 mL of 4N HCl in 1,4-dioxane was added.
Filtration of the white precipitate provided the desired compound as its hydrochloric acid salt. With hydrogenchloride in 1,4-dioxane, diethyl ether Patent; Andersen, Denise Lyn; Chang, Catherine H.; Falsey, James R.; Frohn, Michael J.; Hong, Fang-Tsao; Liao, Hongyu; Liu, Longbin; Lopez, Patricia; Retz, Daniel Martin; Rishton, Gilbert M.; Rzasa, Robert M.; Siegmund, Aaron; Tadesse, Seifu; Tamayo, Nuria; Tegley, Christopher M.; US2006/69110; (2006); (A1) English
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View in Reaxys
N
N
N
H 2N Cl
H
Rx-ID: 2653804 View in Reaxys 3/12 Yield
Conditions & References With hydrogenchloride, triethyl phosphite in dichloromethane, 1.) room temp., overnight, 2.) room temp., overnight, Yield given Koziara, Anna; Osowska-Pacewicka, Krystyna; Zawadzki, Stefan; Zwierzak, Andrzej; Synthesis; nb. 5; (1987); p. 487 489 View in Reaxys
Cl
H 2N Cl
H
Rx-ID: 20385537 View in Reaxys 4/12 Yield
Conditions & References Reaction Steps: 2 1: SnCl4, trimethylsilyl azide / CH2Cl2 / 144 h / 15 - 20 °C 2: 1.) triethyl phosphite, 2.) gas HCl / CH2Cl2 / 1.) room temp., overnight, 2.) room temp., overnight With hydrogenchloride, trimethylsilylazide, tin(IV) chloride, triethyl phosphite in dichloromethane Koziara, Anna; Osowska-Pacewicka, Krystyna; Zawadzki, Stefan; Zwierzak, Andrzej; Synthesis; nb. 5; (1987); p. 487 489 View in Reaxys
H 2N
HN
Cl
H
N
Rx-ID: 3579782 View in Reaxys 5/12 Yield
Conditions & References With hydrogenchloride, hydrogen, 10 wt. % palladium on activated carbon in ethanol, T= 50 °C , p= 760Torr , Yield given Baldwin, Jack E.; Adlington, Robert M.; Newington, Ian M.; Journal of the Chemical Society, Chemical Communications; nb. 2; (1986); p. 176 - 178 View in Reaxys
H 2N Cl
aq.-ethanolic KOH
H
Br
Rx-ID: 19033247 View in Reaxys 6/12 Yield
Conditions & References Reaction Steps: 3 1: 100 percent 2: trifluoroacetic acid / 25 °C 3: conc. aq. HCl, H2 / 10percent Pd/C / ethanol / 50 °C / 760 Torr With hydrogenchloride, hydrogen, trifluoroacetic acid, 10 wt. % palladium on activated carbon in ethanol
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Baldwin, Jack E.; Adlington, Robert M.; Newington, Ian M.; Journal of the Chemical Society, Chemical Communications; nb. 2; (1986); p. 176 - 178 View in Reaxys
H 2N Cl
N
H
N
Rx-ID: 19052010 View in Reaxys 7/12 Yield
Conditions & References Reaction Steps: 2 1: trifluoroacetic acid / 25 °C 2: conc. aq. HCl, H2 / 10percent Pd/C / ethanol / 50 °C / 760 Torr With hydrogenchloride, hydrogen, trifluoroacetic acid, 10 wt. % palladium on activated carbon in ethanol Baldwin, Jack E.; Adlington, Robert M.; Newington, Ian M.; Journal of the Chemical Society, Chemical Communications; nb. 2; (1986); p. 176 - 178 View in Reaxys
H 2N
H N
P
Cl
H
O
Rx-ID: 2588815 View in Reaxys 8/12 Yield
Conditions & References With hydrogenchloride in methanol Buchowiecki, Wieslaw; Grosman-Zjawiona, Zofia; Zjawiony, Jordan; Tetrahedron Letters; vol. 26; nb. 9; (1985); p. 1245 1248 View in Reaxys
O
H N
H 2N Cl
H
Rx-ID: 2086323 View in Reaxys 9/12 Yield
Conditions & References With hydrogenchloride, sodium hydroxide, 1.220 gradC, 24h;, Multistep reaction Dube, Michael F.; Timberlake, Jack W.; Tetrahedron; vol. 36; (1980); p. 1753 - 1756 View in Reaxys
HO
H 2N Cl
H
Rx-ID: 20827683 View in Reaxys 10/12 Yield
Conditions & References Reaction Steps: 2 1: 79 percent / H2SO4, AcOH / Ambient temperature; The reagents were added at 0 gradC, then stirring overnight at room temperature.
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2: 1. 20percent NaOH, 2. HCl gas / 1.220 gradC, 24h; With hydrogenchloride, sodium hydroxide, sulfuric acid, acetic acid Dube, Michael F.; Timberlake, Jack W.; Tetrahedron; vol. 36; (1980); p. 1753 - 1756 View in Reaxys
H 2N Mg
Cl
Cl
H
Rx-ID: 20861292 View in Reaxys 11/12 Yield
Conditions & References Reaction Steps: 3 1: 61 percent 2: 79 percent / H2SO4, AcOH / Ambient temperature; The reagents were added at 0 gradC, then stirring overnight at room temperature. 3: 1. 20percent NaOH, 2. HCl gas / 1.220 gradC, 24h; With hydrogenchloride, sodium hydroxide, sulfuric acid, acetic acid Dube, Michael F.; Timberlake, Jack W.; Tetrahedron; vol. 36; (1980); p. 1753 - 1756 View in Reaxys O
OH
H 2N
1,1,-Dimethyl-2-phenyl-ethylamine
Cl
H
O O
O
Rx-ID: 25282303 View in Reaxys 12/12 Yield
Conditions & References 13 : Methyl 3-benzyloxy-5-[(2-(1,1 dimethyl-2-phenylethylamino)1-hydroxyethyl]-benzoate. EXAMPLE 13 Methyl 3-benzyloxy-5-[(2-(1,1 dimethyl-2-phenylethylamino)1-hydroxyethyl]-benzoate. The 3-benzyloxy-5-carboxyphenylglyoxal (120 mmoles) was dissolved in MeOH (1 l.) and cooled to 0°. 1,1,-Dimethyl-2-phenyl-ethylamine (100 g, 0.67 moles) was added at 0° and the resulting mixture was stirred at 0° for 1 hr. before addition of KBH4 (12.2 g, 228 mmoles) over a period of 2 hrs. portionwise. The resultant mixture was allowed to react at room temperature for 18 hours before it was evaporated to a residual glass. The residue was acidified with 6N HCl (l l.) and extracted with CHCl3 (1 l.). Addition of ether to the CHCl3 extract gave the 1,1-dimethyl-2-phenylethylamine HCl as a white precipitate which was removed by filtration. With KBH4 in methanol Patent; Warner-Lambert Company; US4018825; (1977); (A) English View in Reaxys
Copyright © 2018 Reed Elsevier Properties SA. All rights reserved. Authorized use only. Reaxys® and the Reaxys® trademark are owned and protected by Reed Elsevier Properties SA and used under license.
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