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Method for synthesizing chiral 3-amino-3-phenyl-2-hydroxy carboxylate compound

A technology for hydroxycarboxylic acid esters and compounds is applied in the field of synthesizing chiral 3-amino-3-phenyl-2-hydroxycarboxylic acid ester compounds, and can solve the problems of low final yield, long synthesis steps, difficult preparation and the like, Achieve the effect of difficult preparation and few reaction steps

Inactive Publication Date: 2014-12-03
XIAN MODERN CHEM RES INST
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Problems solved by technology

In the literature, 3-amino-3-phenyl-2-hydroxycarboxylate compounds mainly include α, β unsaturated esters through asymmetric dihydroxylation (J.Org.Chem.1994,59,5104-5105) or ring Oxidation (J.Org.Chem.1990,55,1957-1959) reaction, followed by azide substitution and reduction; these methods have long synthesis steps and low final yield, only 23%, and the raw material is aromatic α , β unsaturated carboxylate, difficult to prepare

Method used

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  • Method for synthesizing chiral 3-amino-3-phenyl-2-hydroxy carboxylate compound

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0018] Add 0.786g (5.72mmol) of nitrobenzyl, 5mL of tetrahydrofuran and 1.24mL (6.3mmol) of ethyl glyoxylate 50% toluene solution into a 25mL round bottom flask, add a magnet, and add 340mg (0.57 mmol) 1-(3,5-ditrifluoromethylphenyl)-3-[(6-methoxy-quinoline-4)-(5-vinyl-1-aza-bridged ring[2.2. 2] Decane-2)-methyl]-thiourea, reacted at room temperature for 18h, evaporated the solvent, and column chromatography (petroleum ether: ethyl acetate 10-5:1) gave a colorless viscous oil as chiral 3 - 1.163 g of ethyl nitro-3-phenyl-2-hydroxycarboxylate, yield 85.1%.

[0019] 1 H NMR (CDCl 3 , 500MHz): δ1.12(t, J=7.5HZ, 3H), 3.18(br, 1H), 4.13-4.23(m, 2H), 4.84(t, J=5.5HZ, 1H), 5.73(d, J=5.5HZ,1H),7.25-7.45(m,3H),7.51-7.53(m,2H).27%ee.

[0020] The result of hydrogen spectrum confirmed that the compound synthesized by the above method was chiral ethyl 3-nitro-3-phenyl-2-hydroxycarboxylate.

Embodiment 2

[0022] Add 0.786g (5.72mmol) of nitrobenzyl, 5mL of tetrahydrofuran and 1.24mL (6.3mmol) of ethyl glyoxylate 50% toluene solution into a 25mL round bottom flask, add a magnet, and add 256mg (0.57 mmol) 1-(1-phenyl-2-dimethylamino-ethyl)-3-(3,5-bistrifluoromethylphenyl)-thiourea, reacted at room temperature for 18h, evaporated the solvent, column layer Analysis (petroleum ether: ethyl acetate 10 ~ 5: 1) to obtain a colorless viscous oil is 3-nitro-3-phenyl-2-hydroxy ethyl carboxylate 1.028g, yield 75.2%; 19%ee .

Embodiment 3

[0024] Add 0.786g (5.72mmol) nitrobenzyl, 5mL tetrahydrofuran and 1.24mL (6.3mmol) ethyl glyoxylate 50% toluene solution into a 25mL round bottom flask, add a magnet, and add 235.4mg ( 0.57mmol) 1-cyclohexyl-3-(2-dimethylamino-1-phenyl-ethyl)-thiourea, 1-(3,5-ditrifluoromethylphenyl)-3-(2- Dimethylamino-cyclohexyl)-thiourea, reacted at room temperature for 18h, evaporated the solvent, and column chromatography (petroleum ether: ethyl acetate 10-5:1) gave a colorless viscous oil as 3-nitro-3- Ethyl phenyl-2-hydroxycarboxylate 1.028g, yield 77.2%; 11% ee.

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Abstract

The invention discloses a method for synthesizing a chiral 3-amino-3-phenyl-2-hydroxy carboxylate compound. The method comprises the following steps: by taking nitrobenzyl and glyoxylate compounds as raw materials, reacting in an organic solvent under the catalysis of chiral organic alkali to prepare a 3-nitro-3-phenyl-2-hydroxy carboxylate compound, and performing reductive acylation to prepare the chiral 3-amino-3-phenyl-2-hydroxy carboxylate compound. According to the method disclosed by the invention, the raw materials are cheap and easily available, few steps are required for preparing the chiral 3-amino-3-phenyl-2-hydroxy carboxylate compound, and the final yield is high; the method is mainly applied to synthesis of a medical intermediate-chiral 3-amino-3-phenyl-2-hydroxy carboxylate compound.

Description

technical field [0001] The invention belongs to the field of pharmaceutical intermediates, in particular to a method for synthesizing chiral 3-amino-3-phenyl-2-hydroxycarboxylate compounds. technical background [0002] Chiral 3-amino-3-phenyl-2-hydroxycarboxylate compounds are an important class of synthetic intermediates that can be used to synthesize the anticancer drug paclitaxel (Bioorg.Med.Chem.Lett.2003,13,2693– 2697). In the literature, 3-amino-3-phenyl-2-hydroxycarboxylate compounds mainly include α, β unsaturated esters through asymmetric dihydroxylation (J.Org.Chem.1994,59,5104-5105) or ring Oxidation (J.Org.Chem.1990,55,1957-1959) reaction, followed by azide substitution and reduction; these methods have long synthesis steps and low final yield, only 23%, and the raw material is aromatic α , β unsaturated carboxylate, more difficult to prepare. Contents of the invention [0003] The technical problem to be solved in the present invention is aimed at the defi...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C233/87C07C231/10
Inventor 杨翠凤林双政王月梅宁斌科王伦徐泽刚卫天琪张媛媛李秉擘王安勇张晓光
Owner XIAN MODERN CHEM RES INST
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