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Method for synthesizing (1R, 2R)-1-p-methyl sulfone phenyl-2-amino-1,3-propanediol

A technology for the synthesis of thiamphenylphenyl and its method, which is applied in the field of synthesis of 1-p-thiamphenylphenyl-2-amino-1,3-propanediol (I), and can solve problems such as lengthy steps and large dosage , to achieve the effect of short route, easy operation and good enantioselectivity

Inactive Publication Date: 2011-04-13
FUDAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

This method uses asymmetric hydroxycyanation and asymmetric induction to construct two chiral centers successively, and the reaction temperature is suitable, and the yield and selectivity are high; Larger dosage

Method used

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  • Method for synthesizing (1R, 2R)-1-p-methyl sulfone phenyl-2-amino-1,3-propanediol
  • Method for synthesizing (1R, 2R)-1-p-methyl sulfone phenyl-2-amino-1,3-propanediol
  • Method for synthesizing (1R, 2R)-1-p-methyl sulfone phenyl-2-amino-1,3-propanediol

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0032] Example 1 P-methylsulfonylbenzaldehyde (18.42 g, 0.10 mol), diphenylmethylamine (18.33 g, 0.10 mol), dichloroethane (200 mL), and anhydrous magnesium sulfate (40.00 g) were dried In the reaction flask, the reaction was carried out at room temperature for 12 hours. After the reaction is completed, filter and recover the solvent under reduced pressure to obtain a colorless oily substance, which is recrystallized with 95% ethanol, and dried to obtain a white crystal, which is compound (III) (9.60 g, 95%), mp: 139~140°C.

[0033] 1H NMR (CDCl 3 , ppm): δ=3.06 (s, 3H, CH 3 ), 5.67 (s, 1H, CH), 7.26 (m, 2H, ArH), 7.24-7.41 (m, 8H, ArH), 8.02 (m, 4H, ArH) 8.49 (s, 1H, NH).

[0034] ESI-MS: (m / z)=350.6 (M + ).

[0035] Two, (2 S , 3 S )-1-Diphenylmethyl-2-ethoxycarbonyl-3-p-sulfonylphenylacridine (IV).

Embodiment 21

[0036] Example 21 Under nitrogen protection, (2 R )-(+)-3,3'-diphenyl-[2,2'-binaphthalene]-1,1'-diol (4.39 g, 0.01 mol), triphenyl borate (11.60 g, 0.04 mol) was placed in a dry reaction flask, 50 ml of toluene was added, heated to 80 °C for 1 hour, and then the toluene was recovered under reduced pressure, kept at 80 °C under vacuum for 0.5 hours, cooled to room temperature, and dissolved in 50 ml of anhydrous toluene. It was added to a suspension of compound (III) (69.8 g, 0.20 mol) in anhydrous toluene (700 ml), stirred at room temperature for 5 minutes, cooled to -20°C, and added dropwise with ethyl diazoacetate (25.08 g, 0.22 mol). ) and continue to react for 6 hours. Then the solvent was recovered under reduced pressure, and the crude product was recrystallized twice with ethanol and water to obtain compound (IV) (59.52 g, 68.3%) as colorless crystals, mp: 122~123°C, optical rotation [α] 25 D = -20.9° (1.05, CHCl 3 ), the ee value is 99.7%.

[0037] 1 H NMR (CDCl ...

Embodiment 22

[0039] Example 22 Under nitrogen protection, (3 R )-(+)-2,2'-diphenyl-[3,3'-diphenanthrene]-4,4'-diol (5.38 g, 0.01 mol), triphenyl borate (11.60 g, 0.04 mol) ) was placed in a dry reaction flask, 50 ml of toluene was added, heated to 80 °C for 1 hour, the solvent was recovered under reduced pressure, and kept at 80 °C under vacuum for 0.5 hours, cooled to room temperature, dissolved in 50 ml of anhydrous toluene, and It was added to a suspension of compound (III) (69.8 g, 0.20 mol) in anhydrous toluene (700 ml), stirred at room temperature for 5 minutes, cooled to -20°C, and added dropwise with ethyl diazoacetate (25.08 g, 0.22 mol). ) and continue to react for 6 hours. Then the solvent was recovered under reduced pressure, and the crude product was recrystallized twice with ethanol and water to obtain compound (IV) (58.20 g, 66.8%) as colorless crystals. The melting point, optical rotation, 1 H NMR and MS were consistent with Example 21.

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Abstract

The invention discloses a method for synthesizing (1R, 2R)-1-p-methyl sulfone phenyl-2-amino-1,3-propanediol, which belongs to the technical field of chemical medicines. The method comprises the following steps: 1. carrying out condensation on p-methylsulphonyl benzaldehyde (II) and primary amine so as to obtain a compound (III); 2. in the presence of a catalyst, carrying out acridine reaction on the compound (III) and ethyl diazoacetate so as to obtain a compound (IV); 3. carrying out reduction on the compound (IV) so as to obtain a compound (V); and 4. in the presence of an acid, carrying out ring-opening reaction and de-protection reaction on the compound (V) by a one-pot method so as to obtain the (1R, 2R)-1-p-methyl sulfone phenyl-2-amino-1, 3-propanediol. The method provided by the invention has the advantages of novel design, simple and short route, mild conditions, good enantioselectivity, high yield, and good industrialized production prospect, and is simple and convenient in operation.

Description

technical field [0001] The invention belongs to the technical field of chemical medicines, in particular to a kind of (1 R ,2 R )-1-p-thiamphenylphenyl-2-amino-1,3-propanediol (I) synthesis method. Background technique [0002] (1 R ,2 R )-1-p-thiamphenicolphenyl-2-amino-1,3-propanediol is a key chiral intermediate in the synthesis of antibiotics such as Thiamphenicol and Fluorfenicol. Its structural formula is as shown in formula (I): [0003] [0004] (Ⅰ). [0005] US Patent No. 3,927,054 describes that the desired (I) can be obtained from p-sulfone benzaldehyde through condensation, esterification, D-tartaric acid resolution, and reduction, as shown below. However, this method adopts a resolution strategy. Although the L-configuration product can be utilized through racemization or configuration inversion, it has the disadvantages of lengthy steps and low yield. [0006] [0007] Hajra et al. (Tetrahedron, 62, 2006, 8959–8965) reported that N-p-methylmercap...

Claims

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Application Information

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IPC IPC(8): C07C317/32C07C315/04
Inventor 陈芬儿汪忠华李峰
Owner FUDAN UNIV
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