Improved Methodology for the Preparation of Chiral Amines

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CO 2 C 2 H 5 N CN base CN O H + N O N 167 168 169 170 Br 2 N O H 2 N O O Br 173 N 172 OCH 3 171 174 NH 2 N NH OCH 3 175 Scheme 4.9. Synthesis of Ezlopipant. 4.1.10. Synthesis of Monomorine: Monomorine alkaloid is a trail pheromone of the widespread pharaoh’s ant Monomorium pharaonis. [8] Synthesis starts by treating amine (125) with 20% titanocene trichloride forming the imidotitanium complex (126). This compound then underwent a [2+2]-cycloaddition with the alkyne to afford intermediate (127). Ring opening and subsequent metathesis. Imine was reduced with diisobutylaluminum hydride providing amine intermediate followed by deprotection and intramolecular reductive amination resulting in the formation of the alkaloid monomorine. 90
O O 125 NH 2 a 93% O O 126 H Bu N Ti Cp Cl H O O Cp Ti Cl 127 N Bu O O N b 95% O O 128 Bu 129 HN Bu c,d,e 72% N (a) Et 3 N, CpTiCl 3 (20% mol); (b) DIBALH; (c) HCl; (d) K 2 CO 3 ; (e) NaCNBH 3 Scheme 4.10. Synthesis of Monomorine: 4.1.11. Synthesis of Ontazolast: Ontazolast is an antiasthmatic drug which acts as leukotrienes synthesis inhibitors. [8] Synthesis starts with the condensation of pyridine 2-aldehyde with the cyclohexylmethyl magnesium bromide forming carbinol which is oxidized with manganese dioxide to afford the ketone. Reductive amination utilizing ammonium formate/formic acid system converts the carbonyl group into the primary amine. The other half of the final product is formed through the reaction of aminotoluol with carbon disulfide in the presence of a base proceeds to the addition product, benzoxazole. The thiol at the 2 position is then replaced by halogen by reaction with phosphorus oxychloride. Combing this part with the primary amine leads to the formation of alkylated product of ontazolast. MgBr OHC N 1. 2. MnO 2 N O HCO 2 NH 4 HCO 2 H NH 2 N NH 2 OH S C S NaOH N O SH POCl 3 N O Cl Scheme 4.11. Synthesis of Ontazolast HN N N 91 O
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Improved Methodology for the Prepar
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This dissertation is dedicated to a
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suppressing alcohol formation and p
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Prof. Mohamed El-Azizi, Prof. Abdel
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Et EtOH EtOAc GC h HPLC HRMS Hz J K
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Table of Contents Abstract. Acknowl
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4.1.5. Synthesis of Emitine 85 4.1.
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Chapter 1 Introduction 1.1. Chiral
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1. Cis-trans or geometric isomers.
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O O O * NH Thalidomide (R)-active a
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One enantiomer may be responsible f
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1.5.1. Synthesis of Enantiomericall
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1.5.2.2. Kinetic Resolution Kinetic
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compound by the auxiliary. The auxi
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1.5.4. Stereoselective Conversion o
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It is estimated that 3000 tonnes (a
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k R R P 1 k rac S k S P 2 Figure 1.
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(S)-(α)-Methylbenzylamine and its
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fourth chapter showing different dr
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Burk was successful in reducing ary
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Table 1.1 Rhodium Catalyzed Reducti
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[8] E. L. Eliel, S. H. Wilen, Stere
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[42] a) J. Blacker, Innovations in
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[67] a) H. Qin, N. Yamagiwa, S. Mat
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of imine reduction in the past eigh
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8 years beginning from the year 200
Page 53 and 54: 2.2.3. Nguyen Special Substrates. A
Page 55 and 56: Figure 2.4 General Catalyst structu
Page 57 and 58: 2.3.2. Different Substrates Categor
Page 59 and 60: H 2 , toluene, 25 °C, 4 h an ee of
Page 61 and 62: 1). They described the role of each
Page 63 and 64: More recently, 2008, he described t
Page 65 and 66: [22] E. Guiu, M. Aghmiz, Y. Diaz, C
Page 67 and 68: Chapter 3 Reductive Amination 3.1.
Page 69 and 70: . CH 3 CO(CH 2 ) 5 CH 3 H 2 NCH 2 C
Page 71 and 72: superior in terms of conversion (89
Page 73 and 74: O NHR 3 R 4 R 4 R 3 N OTi(O i Pr) 3
Page 75 and 76: Scheme 3.9. Synthesis of (S)-Metola
Page 77 and 78: groups decreased both the enantiose
Page 79 and 80: progress of the reaction was monito
Page 81 and 82: attempts were directed for the asym
Page 83 and 84: hydrogen bonding, is chiral and its
Page 85 and 86: Later he utilized this methodology
Page 87 and 88: OMe OMe O HN HN HN O 2 N 71 % yield
Page 89 and 90: compared to the oil refinery indust
Page 91 and 92: [14] V. I. Tararov, R. Kadyrov, T.H
Page 93 and 94: [55] a) R. Kadyrov, T. H. Riermeier
Page 95 and 96: Chapter 4 Drugs and Reductive Amina
Page 97 and 98: Scheme 4.2. Synthesis of Muraglitaz
Page 99 and 100: Studies showed that the active isom
Page 101 and 102: aminoacid producing the protected a
Page 103: O NH 2 1. p-TsOH/toluene 2. BH 3 -T
Page 107 and 108: ethyl carbamate by acylation with e
Page 109 and 110: 4.1.16. Synthesis of Ritonavir and
Page 111 and 112: 4.2. Conclusion Different important
Page 113 and 114: Chapter 5 Stoichiometric Use of Ytt
Page 115 and 116: The unique feature of this methodol
Page 117 and 118: Ytterbium triflate is the most comm
Page 119 and 120: Ruthenium(III) chloride 31.7 4 4.2
Page 121 and 122: t-Butyl methyl ether 15 - - 82 Hexa
Page 123 and 124: 2-octanone starting material. When
Page 125 and 126: 3 Yb(OTf) 3 d 4 Ti(O i Pr) 4 e 5 B(
Page 127 and 128: If a [1,3]-proton shift of the init
Page 129 and 130: enhanced stereoselectivity. For exa
Page 131 and 132: WO2006030017, 2006; c) T. C. Nugent
Page 133 and 134: 4 60 86 5 50 86 6 40 84 7 20 79 8 2
Page 135 and 136: The reactions described above all u
Page 137 and 138: e.g. compare entries 1, 5, 6, and 9
Page 139 and 140: solvent in the stoichiometric and c
Page 141 and 142: [2] Farina, V.; Grozinger, K.; Mül
Page 143 and 144: congested which should be favored.
Page 145 and 146: imine area % (GC analysis) time (mi
Page 147 and 148: Inversion at the nitrogen atom of t
Page 149 and 150: anti-6) would be expected to have m
Page 151 and 152: e.g. AcOH, suppresses alcohol by-pr
Page 153 and 154: eductive amination of a prochiral k
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Appendix Experimental Section Gener
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and the mixture was stirred for 30
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Reaction details: Yb(OAc) 3 (1.1 eq
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etention time [min]: major (S,S)-2b
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time [min]: major (S,S)-2c isomer,
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obtain the hydrochloride salt (0.41
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with etheral HCl provided the hydro
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Research experience: Date Project S
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Improved Methodology for the Preparation of Chiral Amines

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