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(4S, 7RS)-galaxolide synthesis method

A kind of technology of Jiale musk and synthetic method, applied in the direction of organic chemistry method, organic chemistry, etc., can solve the problem of complicated synthetic route and the like

Inactive Publication Date: 2017-05-10
北京安胜瑞力科技有限公司
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] Although there have been several reports on the research on the synthesis of (4S,7RS)-carol musk, the existing methods have problems such as the need for chemical doses of chiral source reagents and cumbersome synthetic routes.

Method used

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Examples

Experimental program
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Embodiment 1

[0018] Synthesis of Pentamethylindane Silane

[0019] Under argon protection, magnesium powder (0.23 g, 9 mmol) was added to a 20 mL Schlenk reaction flask, and dried in vacuum for 2 h. Bromopentamethylindane (0.54g, 2mmol) was added in tetrahydrofuran 2mL, the mixture was heated slowly at 50°C to initiate the reaction, and then the remaining bromopentamethylindane (1.07g, 4mmol) in tetrahydrofuran was slowly added Solution 4mL. After adding the bromide, the reaction mixture was carefully heated to reflux, and continued heating and stirring for 5h to obtain the pentamethylindane Grignard reagent.

[0020] Under argon protection, tetramethoxysilane (2.74 g, 18 mmol) and tetrahydrofuran (10 mL) were added into a 50 mL Schlenk reaction flask, and stirred evenly. The temperature of the mixture was lowered to -30°C, and then 6 mL of a tetrahydrofuran solution of pentamethylindane Grignard reagent was added dropwise. The reaction was stirred at -30°C for 1 h, then slowly warmed t...

Embodiment 2

[0022] Synthesis of (S)-hexamethylindanate

[0023] Under the protection of argon, add NiCl to the 50mL Schlenk reaction flask 2 .glyme (22.0mg, 0.1mmol), [F 2 SiPh 3 ] - [NBu 4 ] + (TBAT, 1080mg, 2.0mmol) and (1S,2S)-N,N-dimethyl-1,2-diphenylethylenediamine (28.8mg, 0.12mmol), then add dioxane (20mL) . The mixture was stirred for 10 min, and pentamethylindansilane (401 mg, 1.3 mmol) and 2-bromopropionic acid-2,6-di-tert-butyl-4-methylphenyl ester (355.3 mg, 1 mmol) were added. The reaction mixture was stirred for 18 h at room temperature. Add a mixed solution of 1M hydrochloric acid and acetone (1:1, 10mL), and stir for 2h. The mixture was poured into water (50 mL), and the organic phase was separated. The aqueous phase was extracted with diethyl ether (3 x 50 mL). The combined organic phases were washed with saturated NaCl solution (50 mL). anhydrous MgSO 4Dry and concentrate under reduced pressure to obtain the crude product. Finally, it was purified by silica ...

Embodiment 3

[0025] Synthesis of (S)-hexamethylindanol

[0026] Under argon protection, add anhydrous CH to a 20 mL Schlenk reaction flask 2 Cl 2 (10 mL), add (S)-hexamethylindanate (1.85 g, 5 mmol), and stir well. The temperature of the mixture was lowered to -78°C, and diisobutylaluminum hydride (DIBAL-H) ​​(7.5 mL, 1.5M solution in toluene, 11 mmol) was added slowly. After the dropwise addition, the stirring reaction was continued at -78°C for 30 minutes, and then the temperature of the reaction mixture was raised to 0°C, and the reaction was stirred for another 30 minutes. After the reaction, the temperature of the reaction mixture was lowered to -78°C, and the reaction was quenched with methanol (1 mL). An aqueous solution of potassium sodium tartrate (22 mL, 0.5 M, 11 mmol) was added, the temperature of the resulting mixture was slowly raised to room temperature, and stirring was continued for 12 h. Separate the organic phase and the aqueous phase with CH 2 Cl 2 (3 x 20 mL) ext...

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Abstract

The invention belongs to the technical field of chemical synthesis of essences and flavors and particularly relates to a (4S, 7RS)-galaxolide synthesis method. The method includes: subjecting bromo-pentamethyl indane and metallic magnesium to reaction to generate a Grignard reagent, and then subjecting to reaction with tetramethoxyl silane to obtain pentamethyl indane silane; subjecting the pentamethyl indane silane to asymmetric Hiyama cross coupling reaction with racemic 2-bromopropionate under catalysis of (1S, 2S)-N,N-dimethyl-1,2-diphenyl diaminoethane and nickel chloride to synthesize (S)-hexamethyl indane acid ester; reducing the (S)-hexamethyl indane acid ester by diisobutyl aluminum hydride (DIBAL-H) to obtain (S)-hexamethyl indanol, and finally subjecting to reaction with paraformaldehyde to obtain (4S, 7RS)-galaxolide. The (4S, 7RS)-galaxolide synthesis method is simple in synthetic route and mild in reaction condition, the overall yield reaches 40%, and product optical purity is 91%.

Description

technical field [0001] The invention belongs to the technical field of chemical synthesis of fragrance essence, and in particular relates to a new method for synthesizing (4S, 7RS)-carole musk. Background technique [0002] Galaxolide is a polycyclic synthetic musk, which was synthesized for the first time by scientists Heeringa and Beets of the International Flavor and Fragrance Company (IFF) in the United States (Heeringa, L.G.; Beets, M.G.J. Patent US3360530, 1967, 12, 26). Jiale musk has many advantages such as strong fragrance, elegant fragrance type, long-lasting fragrance, good stability, and non-toxicity, and is widely used in cosmetics, tobacco flavors, food flavors, etc. , P.; Cruz, A.; Santos, L.; Alves, A. Int. J. Cosmet. Sci. 2013, 35, 299–309.). Frater's research shows that (4S, 7R)-Musk and (4S,7S)-Musk have a strong musky odor, while its diastereoisomers (4R, 7R)-Musk and (4R ,7S) - musk musk is almost odorless (Frater, G.; Muller, U.; Kraft, P. Helv. Chim....

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D311/94
CPCC07D311/94C07B2200/07
Inventor 张国清杨大志袁西福
Owner 北京安胜瑞力科技有限公司
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