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Synthetic method of N-fluorenylmethoxycarbonyl-O-tert-butyl serine

A technology for the synthesis of fluorenylmethoxycarbonyl, which is applied in the field of synthesis of N-fluorenylmethoxycarbonyl-O-tert-butylserine, can solve the problems of high cost, long cycle, and many steps, and shorten the production cycle and process Convenience and easy operation

Active Publication Date: 2008-10-15
南京肽业生物科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0012] A synthesis method of N-fluorenylmethoxycarbonyl-O-tert-butylserine is provided, which mainly solves the problem that the original synthesis method has many steps and a long period, and the route uses flammable, explosive and highly toxic raw materials, and the pollution of three wastes Serious, costly technical problems

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0044] Preparation of serine methyl ester hydrochloride: put 10 kg of serine into 100 kg of anhydrous methanol, feed 15 kg of HCl at room temperature, react for 10 hours, and then distill off the solvent to obtain 13.4 kg of serine methyl ester hydrochloride. The preparation of O-tert-butylserine methyl ester p-toluenesulfonate: 13.4 kilograms of serine methyl ester hydrochloride obtained in the last step join in 200 kilograms of dioxanes, add 80 kilograms of p-toluenesulfonic acid, temperature-5 Add isobutene at ℃, react at 10℃ for 48 hours, and remove the solvent to obtain O-tert-butylserine methyl ester p-toluenesulfonate.

[0045] Preparation of O-tert-butylserine: Put O-tert-butylserine methyl ester p-toluenesulfonate into 320 kg of methanol, add 25 kg of sodium hydroxide aqueous solution, and react for 1 hour at a temperature of 5°C to obtain O- tert-butylserine in methanol in water.

[0046] Preparation of N-fluorenylmethoxycarbonyl-O-tert-butylserine: Add 22.5 kg of F...

Embodiment 2

[0048] Preparation of serine methyl ester hydrochloride: put 80 kg of serine into 800 kg of anhydrous methanol, feed 120 kg of HCl at room temperature, react for 12 hours, and then distill off the solvent to obtain 106 kg of serine methyl ester hydrochloride. Preparation of O-tert-butylserine methyl ester p-toluenesulfonate: 106 kg of serine methyl ester hydrochloride obtained in the previous step is put into 1800 kg of methylene chloride, 632 kg of p-toluenesulfonic acid is added, and isobutylene is added at a temperature of -20°C , followed by reaction at a temperature of 10°C for 72 hours to remove dichloromethane to obtain O-tert-butylserine methyl ester p-toluenesulfonate. Preparation of O-tert-butylserine: Put O-tert-butylserine methyl ester p-toluenesulfonate into 2000 kg of acetone, add 200 kg of sodium hydroxide aqueous solution, and react for 3 hours at a temperature of 5°C to obtain O- tert-butylserine in acetone in water.

[0049] Preparation of N-fluorenylmethoxy...

Embodiment 3

[0051] Preparation of serine methyl ester hydrochloride: put 100 kg of serine into 1000 kg of anhydrous methanol, feed 150 kg of HCl at room temperature, react for 14 hours, and then distill off the solvent to obtain 135 kg of serine methyl ester hydrochloride. The preparation of O-tert-butylserine methyl ester p-toluenesulfonate: 135 kilograms of serine methyl ester hydrochloride that last step obtains joins in 2000 kilograms of dioxanes, after adding 800 kilograms of p-toluenesulfonic acid, temperature-5 Add isobutene at ℃, react at 10℃ for 96 hours, and remove the solvent to obtain O-tert-butylserine methyl ester p-toluenesulfonate.

[0052] Preparation of O-tert-butylserine: Put O-tert-butylserine methyl ester p-toluenesulfonate into 3200 kg of methanol, add 250 kg of sodium hydroxide aqueous solution, and react for 5 hours at a temperature of 5°C to obtain O- tert-butylserine in methanol in water.

[0053]Preparation of N-fluorenylmethoxycarbonyl-O-tert-butylserine: Add ...

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Abstract

The invention relates to a method for synthesizing N-fluorenylmethoxycarbonyl-O-tert-butyl serine which mainly solves the technical problems that: the prior synthetic method has more steps and long period, uses flammable and explosive raw materials with bigger toxicity, and has serious three-waste pollution and high cost. The invention adopts the technical proposal that: the method for synthesizing N-fluorenylmethoxycarbonyl-O-tert-butyl serine comprises the following steps that: a. serine is aerated with HCl gas in anhydrous methanol solvent to react for 10 to 14 hours, and then is distilled to obtain serine methyl ester hydrochloride; b. the serine methyl ester hydrochloride is directly aerated with isobutene, with dioxane or methylene dichloride as solvent under the catalyzing of paratoluenesulfonic acid, to react to obtain O-tert-butyl serine methyl ester; c. the O-tert-butyl serine methyl ester is directly saponified to obtain O--tert-butyl serine; d. and the O-tert-butyl serine is reacted with Fmoc-Cl or Fmoc-osu for 2 to 5 hours to obtain the N-fluorenylmethoxycarbonyl-O-tert-butyl serine. The obtained product of the invention is the important raw material for synthesizing polypeptide.

Description

Technical field: [0001] The invention relates to a method for synthesizing N-fluorenylmethoxycarbonyl-O-tert-butylserine. The obtained N-fluorenylmethoxycarbonyl-O-tert-butylserine is a very important raw material for synthesizing polypeptides. Background technique: [0002] The synthetic route of synthesizing N-fluorenylmethoxycarbonyl-O-tert-butylserine at present is as follows: [0003] a. Serine is passed into HCl gas in anhydrous methanol solvent, and after reacting for 12 hours, distilling obtains serine methyl ester hydrochloride; [0004] b. Serine methyl ester hydrochloride reacts with benzyloxycarbonyl chloride at room temperature to obtain N-benzyloxycarbonyl-serine methyl ester; [0005] c. N-benzyloxycarbonyl-serine methyl ester is passed into isobutylene gas under the catalysis of sulfuric acid, and dichloromethane or dioxane is used as a solvent to react for 96 hours to obtain N-benzyloxycarbonyl-O-tert-butylserine methyl ester ; [0006] d. N-benzyloxycarb...

Claims

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Application Information

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IPC IPC(8): C07C271/22C07C269/04
Inventor 徐红岩付等良朱银
Owner 南京肽业生物科技有限公司