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9 reactions in Reaxys
2018-05-27 13h:55m:41s (UTC)
Cl
O
1. Query
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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.
1/5
2018-05-27 13:57:33
Cl 2H
2H
Br
Cl 2H
2H
N
O
Mg 2H
2H
2H 2H
2H
2H
2H
2H
2H
2H 2 2H
H
2
2
H
H
Rx-ID: 42637109 View in Reaxys 1/9 Yield
Conditions & References 8 : Example 8 Nonstereoselective Synthesis of Deuterated Norketamine Example 8 Nonstereoselective Synthesis of Deuterated Norketamine Scheme 2 The synthesis was conducted following a general reaction sequence as described by Parcell, 1981 (Scheme 2). In the first step, o-chlorobenzonitrile is reacted with cyclopentyl magnesium bromide (obtained by bromination of the commercially available cyclopentane-dio to give cyclopentane bromide -dg 6 and then by Grignard reaction) to give deuterated 1-chlorophenyl-cyclopentyl ketone 7, followed by alpha- bromination of the ketone to give 8, and then reaction with ammonia to form an alpha- hydroxy imine l-hydroxycyclopentyl-(l-chlorophenyl)-ketone-N-methylimine 9. Thermal rearrangement with ring expansion of 9 leads to racemic norketamine 10 with overall yield of 70percent. NMR and MS-spectroscopy confirmed the identity of the products. , Grignard Reaction Patent; AMORSA THERAPEUTICS, INC.; NIVOROZHKIN, Alex; LANDRAU, Nelson; (144 pag.); WO2016/73653; (2016); (A1) English View in Reaxys
Cl
Cl
Br
O
N
Rx-ID: 36532933 View in Reaxys 2/9 Yield 68 %
Conditions & References Racemic norketamine hydrochloride was prepared starting from 2-chlorobenzonitrile.Treatment with cyclopentylmagnesium bromide in the presenceof copper (I) bromide, followed by hydrolysis, gave the cyclopentyl-(2-chlorophenyl) ketone (Weiberth and Hall, 1987). This was brominated with N-bromosuccinimide,followed by treatment with liquid ammonia to form animine intermediate. Thermal rearrangement of the imine afforded (R,S)-norketamine (Fig. 1). The structures of these chemicals were confirmed by1H and 13C NMR spectra with use of a Varian Gemini (300 MHz) instrument(Agilent Technologies, Mulgrave, VIC, Australia). NMR spectra were recordedin CDCl3 solution using tetramethylsilane (0 ppm) and CDCl3 (77.0 ppm) asinternal standards for 1H and 13C, respectively. Optical resolution of theenantiomers was accomplished through formation of the diastereomeric tartratesalts (Hong and Davisson, 1982). Stage 1: With iodine, magnesium in diethyl ether, Time= 1h Stage 2: With copper(I) bromide in diethyl ether, Time= 16h Stage 3: With water Li, Yibai; Coller, Janet K.; Hutchinson, Mark R.; Klein, Kathrin; Zanger, Ulrich M.; Stanley, Nathan J.; Abell, Andrew D.; Somogyi, Andrew A.; Drug Metabolism and Disposition; vol. 41; nb. 6; (2013); p. 1264 - 1272 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.
2/5
2018-05-27 13:57:33
Cl 2H
Cl
Br
2
2
H
H
2H
O 2H
2H
2H
N 2H
2H
2H 2
H
2H
2
H
2H 2
H
2H
2
H
2
H
Rx-ID: 28008059 View in Reaxys 3/9 Yield
Conditions & References 1.1 :The procedure of Step 1 is carried out as described in U.S. Pat. No. 3,254,124. d9-Cyclopentylbromide (about 120 g; available commercially from Sigma-Aldrich, St. Louis Mo. 63103) and magnesium turnings (about 19.4 g) are used to make the corresponding Grignard reagent, which is then reacted with 2-chlorobenzonitrile for about 3 days and hydrolyzed using d1-hydrochloric acid in deuterium oxide to give the title product. Stage 1: With magnesium, Time= 72h Stage 2: With hydrogen chloride in water-d2 Patent; AUSPEX PHARMACEUTICALS, INC.; US2008/268071; (2008); (A1) English View in Reaxys
Cl 2H
2H
Br
Cl 2H
2H
N
O
Mg 2H
2H
2H
2H
2H
2H
2H 2H
2H
2H 2H
2H
2H
Rx-ID: 28008060 View in Reaxys 4/9 Yield
Conditions & References 3.1 :d9-Cyclopentylbromide (2 g, 13.4 mmol) and magnesium turnings (1.85 g, 77.1 mmol) were used to make the corresponding Grignard reagent, which was then mixed with 2-chlorobenzonitrile (1.85 g, 13.2 mmol), copper (I) bromide (100 mg, 0.7 mmol) and diethyl ether (40 mL). The mixture was heated at reflux for about 16 hours and then hydrolyzed for about 2 hours at ambient temperature using 6N hydrochloric acid (10 mL). After standard extractive workup, the crude product was purified by column chromatography on silica gel (petroleum ether-ethyl acetate=70/1, v/v, elution) to give the title product. 1H NMR (300 MHz, CDCl3) δ 7.69-7.26 (m, 4H), 3.55 (s, 1H); LC-MS: m/z=217 (MH)+. Stage 1: With copper(I) bromide in diethyl ether, Time= 16h, Heating / reflux Stage 2: With hydrogenchloride in diethyl ether, water, Time= 2h, T= 20 °C Patent; AUSPEX PHARMACEUTICALS, INC.; US2008/268071; (2008); (A1) English View in Reaxys
Cl
Cl
O
O
Rx-ID: 3474670 View in Reaxys 5/9 Yield 60 %
Conditions & References With hydrogen Zhang, Pang; Li, Lian-chu; Synthetic Communications; vol. 16; nb. 8; (1986); p. 957 - 966 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.
3/5
2018-05-27 13:57:33
Cl
O
N
O
Rx-ID: 19186857 View in Reaxys 6/9 Yield
Conditions & References Reaction Steps: 3 1: Et3N / CHCl3 / 1 h 2: 46.9 percent / H2 / Adams' PtO2 / 0.5 h 3: 60 percent / H2 With hydrogen, triethylamine, platinum(IV) oxide in chloroform Zhang, Pang; Li, Lian-chu; Synthetic Communications; vol. 16; nb. 8; (1986); p. 957 - 966 View in Reaxys
Cl
Cl O
O
Cl
Rx-ID: 19199045 View in Reaxys 7/9 Yield
Conditions & References Reaction Steps: 3 1: Et3N / CHCl3 / 1 h 2: 46.9 percent / H2 / Adams' PtO2 / 0.5 h 3: 60 percent / H2 With hydrogen, triethylamine, platinum(IV) oxide in chloroform Zhang, Pang; Li, Lian-chu; Synthetic Communications; vol. 16; nb. 8; (1986); p. 957 - 966 View in Reaxys
Cl
Cl
O
O
O N
Rx-ID: 19213053 View in Reaxys 8/9 Yield
Conditions & References Reaction Steps: 2 1: 46.9 percent / H2 / Adams' PtO2 / 0.5 h 2: 60 percent / H2 With hydrogen, platinum(IV) oxide Zhang, Pang; Li, Lian-chu; Synthetic Communications; vol. 16; nb. 8; (1986); p. 957 - 966 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.
4/5
2018-05-27 13:57:33
Cl
O
Rx-ID: 7026806 View in Reaxys 9/9 Yield
Conditions & References o-Chlorbenzonitril, Cyclopentylmagnesiumbromid Patent; Stevens; BE634208; (1962); ; vol. 61; nb. 5569c; (1964) View in Reaxys o-Cl-Benzonitril, Cyclopentyl-MgBr Patent; Parke; Davis and Co.; US3254124; (1966); ; vol. 65; nb. 5414g; (1966) View in Reaxys Cyclopentyl-MgBr, o-Chlorbenzonitril Patent; Parke; Davis and Co.; CH454128; (1963); Chem. Zentralbl. 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.
5/5
2018-05-27 13:57:33