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Synthesis of 2',3'-didesoxy-3'-deoxythymidine

A technology for the synthesis of dideoxythymidine, which is applied in chemical recovery, sugar derivatives, organic chemistry, etc., can solve the problems of low catalyst activity, expensive raw materials, and difficult recovery of solvents, and shorten the reaction time and shorten the reaction time , Catalyst cost reduction effect

Inactive Publication Date: 2007-09-05
陆咏
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0004] The present invention proposes a synthesis method of 2', 3'-dideoxy-3'-deoxythymidine, which solves the technical problems of the existing synthesis method that the solvent is difficult to recover, the catalyst activity is low, the process is complicated, and the raw material price is expensive

Method used

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  • Synthesis of 2',3'-didesoxy-3'-deoxythymidine

Examples

Experimental program
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Effect test

Embodiment 1

[0019] Example 1: Dissolve 20Kg of NaOH in 600L of low-carbon alcohol, stir until fully dissolved, then add 60Kg of intermediate (2', 3'-dideoxy-2', 2'-dideoxythymidine), 40 React at -50°C for 1h. The solvent was recovered under reduced pressure, and the residue was recrystallized from a mixed solvent of ethanol-benzene. After cooling, standing still, filtering and drying, 57 kg of white powdery crystalline solid stavudine was obtained, with a yield of 95%. mp166-167°C. Literature mp165-167°C. The content determined by HPLC (area normalization method) is 99.6%. UV spectrum

[0020] λmax266nm, ξ=13.6×10 3 , λmax235nm, ξ=3.32×10 3， , MS mass spectrum m / EC 10 h 12 N 2 o 4 =224(M + ); NMR HNMR (DMSO-d6) £: 1.71 (s, 3H, CH 3 ), 3.59-3.62 (m, 2H, H-5′), 4.76 (s, 1H, H-4′), 5.02 (s, 1H, OH), 5.90 (d, j=5.7H 2 , 1H, H-2'), 6.38 (d, j=5.7H 2 , 1H, H-3'), 6.80-6.83 (m, 1H, H-1'), 7.64 (s, 1H, H-6), 11.37 (S, 1H, NH). The product was proved to be stavudine.

Embodiment 2

[0021] Example 2: Dissolve 20Kg of NaOH in 600L of THF (tetrahydrofuran), stir until fully dissolved, then add 60Kg of intermediate, and react at 40-50°C for 1h. The solvent was recovered under reduced pressure, and the residue was recrystallized from a mixed solvent of ethanol-benzene. After cooling, standing, filtering and drying, 56.4 kg of white powdery crystalline solid stavudine was obtained, with a yield of 94%. mp166-167°C. Literature mp165-167°C. The content determined by HPLC (area normalization method) is 99.7%. UV spectrum

[0022] λmax266nm, ξ=13.6×10 3 , λmax235nm, ξ=3.32×10 3， , MS mass spectrum m / EC 10 h 12 N 2 o 4 =224(M + ); NMR HNMR (DMSO-d6) £: 1.71 (s, 3H, CH 3 ), 3.59-3.62 (m, 2H, H-5′), 4.76 (s, 1H, H-4′), 5.02 (s, 1H, OH), 5.90 (d, j=5.7H 2 , 1H, H-2'), 6.38 (d, j=5.7H 2 , 1H, H-3'), 6.80-6.83 (m, 1H, H-1'), 7.64 (s, 1H, H-6), 11.37 (S, 1H, NH). The product was proved to be stavudine.

Embodiment 3

[0023] Example 3: Dissolve 20Kg of NaOH in 600L of ethanol, stir until fully dissolved, then add 60Kg of intermediate, and react at 40-50°C for 1h. The solvent was recovered under reduced pressure, and the residue was recrystallized from a mixed solvent of ethanol-benzene. After cooling, standing still, filtering and drying, 57.6 kg of white powdery crystalline solid stavudine was obtained, with a yield of 96%. mp166-167°C. Literature mp165-167°C. The content determined by HPLC (area normalization method) is 99.2%. UV spectrum

[0024] λmax266nm, ξ=13.6×10 3 , λmax235nm, ξ=3.32×10 3， , MS mass spectrum m / EC 10 h 12 N 2 o 4 =224(M + ); NMR HNMR (DMSO-d6) £: 1.71 (s, 3H, CH 3 ), 3.59-3.62 (m, 2H, H-5′), 4.76 (s, 1H, H-4′), 5.02 (s, 1H, OH), 5.90 (d, j=5.7H 2 , 1H, H-2'), 6.38 (d, j=5.7H 2 , 1H, H-3'), 6.80-6.83 (m, 1H, H-1'), 7.64 (s, 1H, H-6), 11.37 (S, 1H, NH). The product was proved to be stavudine.

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Abstract

A process for synthesizing 2',3'-dideoxy-3'-deoxythymidine includes such steps as preparing the intermediate, 2,3'-dideoxy-2',2'-bideoxythymidine, dissolving catalyst in solvent, adding said intermediate, reacting at 40-50 deg.C for 1 hr, vacuum recovery of solvent, and recrystallizing.

Description

technical field [0001] The invention relates to a method for synthesizing 2', 3'-dideoxy-3'-deoxythymidine. Background technique [0002] 2',3'-dideoxy-3'-deoxythymidine (commonly known as stavudine) is a new anti-AIDS drug with high efficiency, low toxicity and low price. There are many patent documents and synthesis methods, but in recent years, due to the national policy of restricting the price of anti-AIDS drugs. It is required that the synthesis of raw materials must reduce the cost significantly in order to meet the large demand of the market. The commonly used synthetic method is to add 2', 3'-dideoxy-2', 2'-dideoxythymidine into dimethyl sulfoxide, then add potassium tert-butoxide, stir for 10 hours, and evaporate di Methyl sulfoxide was obtained as a crude product. The crude product was recrystallized from acetone. The high boiling point solvent dimethyl sulfoxide (189°C) is used in the last step of the elimination reaction. Due to the high boiling point of thi...

Claims

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Application Information

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IPC IPC(8): C07H19/073
CPCY02P20/584
Inventor 陆咏
Owner 陆咏