Preparation method of 2-tert-butyl-7-methyl-5-oxa-2,8-diazaspirane-[3,5]nonane-2,7-dicarboxylic acid

An azaspirane, tert-butyl technology, applied in 2-tert-butyl-7-methyl-5-oxa-2,8-diazaspirane-[3,5]nonane-2 , The field of preparation of 7-dicarboxylic acid can solve the problems of no suitable industrial synthesis method, and achieve the effects of saving purification time and consumption, easy reaction and convenient operation

CN106831818AInactive Publication Date: 2017-06-13SHANGHAI SYNTHEALL PHARM CO LTD
2 Cites 0 Cited by

Patent Information

Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Publication Date
2017-06-13
Estimated Expiration
Not applicable · inactive patent

Smart Images

  • Figure 1
    Figure 1
  • Figure 2
    Figure 2
  • Figure 3
    Figure 3
Patent Text Reader

Abstract

The invention relates to a synthesis method of 2-tert-butyl-7-methyl-5-oxa-2,8-diazaspirane-[3,5]nonane-2,7-dicarboxylic acid, aiming at mainly solving the technical problem that a suitable industrial synthesis method does not exist at present. The synthesis method is divided into four steps as follows: firstly, taking a compound 1 to react with n-butyl lithium and benzyl chloroformate in tetrahydrofuran to obtain a compound 2; then, taking the compound 2 to react with diphenyl chlorophosphate and lithium hexamethyldisilazide to obtain a compound 3; inserting carbonyl into the compound 3 in the presence of CO under the action of palladium acetate and triphenylphosphine to obtain a compound 4; under the action of hydrogen and palladium on carbon, carrying out hydrogenation reduction again to obtain a target compound 5. A formula is shown I in the description. The compound prepared by the synthesis method is a useful immediate or product synthesized by a plurality of medicines.
Need to check novelty before this filing date? Find Prior Art

Description

technical field

[0001] The invention relates to a synthesis method of 2-tert-butyl-7-methyl-5-oxa-2,8-diazaspirane-[3,5]nonane-2,7-dicarboxylic acid. Background technique

[0002] 2-tert-butyl-7-methyl-5-oxa-2,8-diazaspirone-[3,5]nonane-2,7-dicarboxylic acid and related derivatives in medicinal chemistry and Widely used in organic synthesis. At present, there is no literature report on the synthesis of 2-tert-butyl-7-methyl-5-oxa-2,8-diazaspirane-[3,5]nonane-2,7-dicarboxylic acid. There is a certain risk in similar literature reactions, and the route is long and the yield is low. Therefore, it is necessary to develop a synthetic method with readily available raw materials, convenient operation, easy control of the reaction, and suitable overall yield. Contents of the invention

[0003] The purpose of the present invention is to develop a kind of 2-tert-butyl-7-methyl-5-oxa-2,8-diazaspirane that has raw material easy to get, easy to operate, easy to control reaction and ...

Examples

Embodiment 1

[0010] Example 1: a. Compound 1 (430g, 1.77mol) was dissolved in 3L of tetrahydrofuran, under the protection of nitrogen, the reaction temperature was controlled at -78°C to -50°C, and n-butyllithium (125g, 1.95 mol). After the dropwise addition, the reaction temperature was maintained and stirring was continued for 1-2 hours. Benzyl chloroformate (322.8 g, 1.86 mol) was dissolved in 1 L of tetrahydrofuran, and the reaction temperature was controlled at -78°C to -50°C, and added dropwise to the reaction solution. After the dropwise addition, the reaction temperature was maintained and stirring was continued for 2-4 hours. TLC (petroleum ether / ethyl acetate volume ratio=2 / 1) showed that the reaction was complete. The reaction solution was poured into saturated aqueous ammonium chloride (5 L), and extracted with ethyl acetate (3 L x 3). The organic phases were combined, dried over sodium sulfate, filtered, and concentrated by distillation under reduced pressure to obtain a cr...

Embodiment 2

[0015] Example 2: a. Compound 1 (4300g, 17.7mol) was dissolved in 25L of tetrahydrofuran, under the protection of nitrogen, the reaction temperature was controlled at -78°C to -50°C, and n-butyllithium (1250g, 19.5 mol). After the dropwise addition, the reaction temperature was maintained and stirring was continued for 1-2 hours. Benzyl chloroformate (3228 g, 18.6 mol) was dissolved in 5 L of tetrahydrofuran, and the reaction temperature was controlled at -78°C to -50°C, and added dropwise to the reaction solution. After the dropwise addition, the reaction temperature was maintained and stirring was continued for 2-4 hours. TLC (petroleum ether / ethyl acetate volume ratio=2 / 1) showed that the reaction was complete. The reaction solution was poured into saturated aqueous ammonium chloride solution (35 L), and extracted with ethyl acetate (15 L x 3). The organic phases were combined, dried over sodium sulfate, filtered, and concentrated by distillation under reduced pressure t...