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6 reactions in Reaxys
2018-06-09 08h:45m:03s (UTC)
H 2N
1. Query F
Search as: Product, As drawn, No mixtures ))
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F
H 2N
F
O
NH
Rx-ID: 47789051 View in Reaxys 1/6 Yield
Conditions & References 4.3.2 : Step 3 Synthesis of 1-(4-fluorophenyl)-2-methyl-2-propylamine The aqueous solution of N-[1-(4-fluorophenyl)-2-methylprop-2-yl]acetamide and potassium hydroxide prepared in the second step was added to the autoclave and replaced with nitrogen. The reaction was maintained at the temperature. The reaction was completed and the system was an oil-water phase. The pale yellow oil layer was separated into crude product 1-(4-fluorophenyl)-2-methyl-2-propylamine. With water, potassium hydroxide, Time= 22h, T= 200 - 220 °C , Autoclave, Inert atmosphere, Temperature Patent; Dalian Jiu Xin Fine Chemical Co., Ltd.; Wang Naiwei; Jiang Renwu; Sun Yuqin; Qin Xuekong; (7 pag.); CN101704756; (2017); (B) Chinese View in Reaxys
H 2N
F Cl
F
Rx-ID: 47789052 View in Reaxys 2/6 Yield
Conditions & References Reaction Steps: 3 1.1: magnesium / toluene; tetrahydrofuran / 5 - 10 °C 1.2: 10 - 20 °C 2.1: sulfuric acid / 40 - 45 °C 3.1: potassium hydroxide; water / 22 h / 200 - 220 °C / Autoclave; Inert atmosphere With sulfuric acid, water, magnesium, potassium hydroxide in tetrahydrofuran, toluene Patent; Dalian Jiu Xin Fine Chemical Co., Ltd.; Wang Naiwei; Jiang Renwu; Sun Yuqin; Qin Xuekong; (7 pag.); CN101704756; (2017); (B) Chinese View in Reaxys
H N
O O
F O F
N H
NH N H
O
O
OH
HO O
H 2N
O
O
O
F
HN
OH
OH H
Rx-ID: 27768834 View in Reaxys 3/6
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Yield
Conditions & References 6.5 :The acid degradation mechanism is hydrolysis of the two amide bonds.Hydrolysis of the first amide bond yields fragments of MW (molecular weight) 167 and MW 327. Hydrolysis of the second amide bond yields fragments of MW 198 and MW 278. The MW 327 degradant can further hydrolyze to a fragment of MW 198. These two degradants (MW198 and MW327) were isolated by semi-prep HPLC and characterized by LC-MS and NMR. The molecular structures for the two major degradants have been confirmed based on exact mass, NMR, LC-MS fragmentation patterns, and HPLC relative retention times. The proposed degradation pathway is shown in Figure 21. With hydrogenchloride, water in acetonitrile, Time= 240h, T= 90 °C Patent; WYETH; WO2008/58278; (2008); (A2) English View in Reaxys
H N
Cl
H 2N H
Cl
O F
F
Rx-ID: 10697828 View in Reaxys 4/6 Yield
Conditions & References 3 :A solution of chloro-N-[2-(4-fluorophenyl)-l,l-dimethylethyl]acetamide(71.4 g, 0.293 mol) in ethanol (125 ml) and acetic acid (55 ml) was added dropwise to a stirred suspension of thiourea (26.7 g, 0.351 mol) in ethanol (125 ml) at about 78 - 86°C. The resulting mixture was allowed to stir at about 80 - 860C for about 4 hours. The reaction was monitored for completion by HPLC. [0072] When the reaction was complete, the mixture was cooled to about 20 -250C and then filtered. The reaction flask and filter cake were rinsed with ethanol, and then the filtrate was concentrated under vacuum. Water (about 200 ml) and toluene (about 200 ml) were added and the phases were thoroughly mixed. The phases were separated, and the upper organic phase was discarded. Toluene (about 400 ml) was added to the lower aqueous phase, and the resulting mixture was cooled to about 5 - 100C. Sodium hydroxide solution (50percent w/w, about 50 ml) was added dropwise to adjust the pH of the aqueous phase to about 13 - 14. The phases were separated, and then the upper organic layer was washed with water. Hydrochloric acid solution (37percent, 53 g, 44 ml, 0.44 mol) was added to the organic solution, and then the mixture was concentrated under vacuum to approximately 500 ml volume. During the concentration, water was removed, and the product began to precipitate. The product mixture was cooled to about 150C and then filtered. The product cake was rinsed with toluene and then dried to give 2-(4- <n="49"/>fluorophenyl)- 1,1-dimethylethylamine hydrochloride (43.6 grams, 87percent HPLC area). HPLC Retention time = 4.6 min. 1H NMR: (DMSO-</6, with 2 drops D2O, 300 MHz): δ 7.31 - 7.16 (m, 4H), 2.86 (s, 2 H), 1.20 (s, 6H). Stage 1: With thiourea in ethanol, acetic acid, Time= 4h, T= 78 - 86 °C Stage 2: With hydrogenchloride in water, toluene Patent; WYETH; WO2007/143014; (2007); (A2) English View in Reaxys
O
F Si
N
O
H 2N H
dimethylparafluorobenzylmethanamine hydrochloride
Cl
F
Rx-ID: 24586496 View in Reaxys 5/6 Yield 60%
Conditions & References 5.C : Step C. Step C. Dimethyl-4-fluorobenzylmethanamine.hydrochloride A mixture of N-[(dimethyl-4-fluorobenzylsilyl)methyl]phthalimide (2.90 g, 8.88 mmol) and hydrazine hydrate (0.53 g, 10.66 mmol) in ethanol (30 ml) was refluxed for 3 hours. 6N HCl (7 ml) was added and refluxing was continued for 30 minutes. Then the mixture was cooled, filtered and evaporated.
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Purification of the hydrochloride salt was achieved via its N-Boc derivative. Dimethylparafluorobenzylmethanamine hydrochloride was obtained as a white powder by cleavage of the N protecting group using the method described in Step D. of Example 13. (1.25 g, 60percent yield) mp 134°-135° C. 1H NMR (CDCl3, TMS) δ: 0.20 (s,6H), 2.27 (s,2H), 2.30-2.57 (m,2H), 6.77-7.00 (m,4H), 8.07 (broad s, 3H). With hydrogenchloride, hydrazine hydrate in ethanol Patent; Merrell Pharmaceuticals Inc.; US5532397; (1996); (A) English View in Reaxys
H 2N
F
Rx-ID: 7788129 View in Reaxys 6/6 Yield
Conditions & References Patent; Troponwerke Dinklage; DE1199779; (1965); ; vol. 63; nb. 17967a; (1965) View in Reaxys Patent; Societe Wagentaise; FRM4288; (1964); ; vol. 68; nb. 59250p; (1968) View in Reaxys Patent; Tropon; GB1037027; (1966); ; vol. 65; nb. 12136h; (1966) View in Reaxys Patent; Troponwerke Dinklage; NL6503967; (1966); ; vol. 66; nb. 55205 View in Reaxys Patent; Troponwerke Dinklage andCo.; FRM4578; (1965); ; vol. 69; nb. 86593e; (1968) View in Reaxys Patent; Troponwerke Dinklage; FRCAM66; (1963); ; vol. 62; nb. 13087g; (1965) View in Reaxys Patent; Science Union et Cie-Soc. Francaise de Recherches Medicales; BE609630; (1960); ; vol. 60; nb. 1647b; (1964) View in Reaxys
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