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Synthesis method of multi-configuration O-phenyl-serine compound

A synthesis method and compound technology, applied in the field of organic compound synthesis, can solve the problems of violent reaction, low safety, complicated operation, etc., and achieve the effects of mild reaction, simple reaction and easy operation, and high product yield.

Active Publication Date: 2020-06-26
苏州爱玛特生物科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] In the synthetic method about this type of compound announced now, usually can adopt triphenylphosphine as catalyst, DIAD (diisopropyl azodicarboxylate) etc. to participate in reaction (as references: Castelli R, Tognolini M, Vacondio F, et al.Δ5-Cholenoyl-amino acids as selective and orally available antagonists of the Epheephrin system[J].European Journal of Medicinal Chemistry,2015,103:312-324.), not only the method is single, the reaction is violent, and it needs to be controlled at low temperature Carried out, the effect is poor, the yield is low
Moreover, triphenylphosphine is irritating to the eyes, upper respiratory tract, mucous membranes and skin, and has neurotoxic effects. The operation should be standardized, so the operation is cumbersome and the safety is low.

Method used

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  • Synthesis method of multi-configuration O-phenyl-serine compound
  • Synthesis method of multi-configuration O-phenyl-serine compound
  • Synthesis method of multi-configuration O-phenyl-serine compound

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0032] Synthesis of O-phenyl-DL-serine

[0033]

[0034] Under nitrogen protection, iodobenzene (2.0g, 10mmol), N-tert-butoxycarbonyl-DL-serine methyl ester (2.2g, 10mmol) were dissolved in DMF (50mL), and K 2 CO 3 (0.2g, 1.0mmol), bis(triphenylphosphine) palladium dichloride (PdCl 2 (P(C 6 h 5 ) 3 ) 2 ) (1.4mg, 2.0mmol%), heated and stirred at 80°C for 6h, after the reaction, extracted with ethyl acetate, dried over anhydrous magnesium sulfate, removed most of the solvent in the reaction solution, purified by silica gel column chromatography, dichloromethane After the intermediate was obtained by elution with methanol / methanol (V / V=20 / 1), 6N HCl (80mL) was added, and the reaction was stirred overnight at room temperature. 2 O, recrystallized from petroleum ether to obtain O-phenyl-DL-serine (1.6g). Yield: 88%.

[0035] 1 H NMR (400MHz, CDCl 3 )δ7.28(m,2H),6.97(tt,1H),6.91(m,2H),5.04(dd,1H),4.77(dd,1H),4.35(d,2H),3.92(tt,1H ).

[0036] 13 C NMR (125MHz, CDCl 3...

Embodiment 2

[0038] Synthesis of O-phenyl-D-serine

[0039]

[0040]The raw materials of this example are iodobenzene (10mmol) and N-tert-butoxycarbonyl-D-serine methyl ester (10mmol). Others are the same as Example 1, and the product yield is 86%.

[0041] 1 H NMR (400MHz, CDCl 3 )δ7.28(m,2H),6.97(tt,1H),6.91(m,2H),5.04(dd,1H),4.77(dd,1H),4.35(d,2H),3.92(tt,1H ).

[0042] 13 C NMR (125MHz, CDCl 3 )δ173.63(dd), 159.36(m), 129.56(dt), 121.10(tq), 115.23(dt), 67.42(t), 55.26(dd).

Embodiment 3

[0044] Synthesis of O-phenyl-L-serine

[0045]

[0046] The raw materials of this example are iodobenzene (10mmol) and N-tert-butoxycarbonyl-L-serine methyl ester (10mmol). Others are the same as Example 1, and the product yield is 87%.

[0047] 1 H NMR (400MHz, CDCl 3 )δ7.28(m,2H),6.97(tt,1H),6.91(m,2H),5.04(dd,1H),4.77(dd,1H),4.35(d,2H),3.92(tt,1H ).

[0048] 13 C NMR (125MHz, CDCl 3 )δ173.63(dd), 159.36(m), 129.56(dt), 121.10(tq), 115.23(dt), 67.42(t), 55.26(dd).

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Abstract

The invention relates to a synthesis method of a multi-configuration O-phenyl-serine compound. The method comprises the following steps: (1) in the presence of a solvent, alkali and a palladium catalyst, reacting a compound shown as formula I and a compound shown as formula II under the protection of inert gas to obtain an intermediate compound; (2) carrying out deprotection reaction on the intermediate compound to prepare an O-phenyl-serine compound shown as formula III; wherein the structural formula of the compound shown as formula I is shown in the specification, the structural formula ofthe compound shown as formula II is shown in the specification, and the structural formula of the compound shown as formula III is shown in the specification, wherein in the formula I and formula III,R is one of H, alkyl, alkoxy and halogen. According to the synthesis method disclosed by the invention, the palladium catalyst is selected as the catalyst, so that the reaction of mono-substituted iodobenzene and multi-configuration N-tert-butyloxycarbonyl-serine methyl ester can be effectively catalyzed, the reaction is promoted, the reaction is simple and easy to operate, mild, low in toxicity,and high in product yield.

Description

technical field [0001] The invention belongs to the technical field of organic compound synthesis, and in particular relates to a synthesis method of multi-configuration O-phenyl-serine compounds. Background technique [0002] O-phenyl-serine compounds based on monosubstituted benzene rings are an important class of pharmaceutical intermediates and are widely used in the field of medicinal chemistry. For example, as an intermediate in the synthesis of drugs such as chemotherapeutic agents for the treatment of tumors. [0003] In the synthetic method about this type of compound announced now, usually can adopt triphenylphosphine as catalyst, DIAD (diisopropyl azodicarboxylate) etc. to participate in reaction (as references: Castelli R, Tognolini M, Vacondio F, et al.Δ5-Cholenoyl-amino acids as selective and orally available antagonists of the Epheephrin system[J].European Journal of Medicinal Chemistry,2015,103:312-324.), not only the method is single, the reaction is violen...

Claims

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Application Information

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IPC IPC(8): C07C227/20C07C229/22C07C269/06C07C271/22
CPCC07C227/20C07C269/06C07C271/22C07C229/22Y02P20/55
Inventor 汪明中朱明新苏道李金金
Owner 苏州爱玛特生物科技有限公司
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