Preparation method of optically-active 7-halogenated-6-hydroxyheptane-3-ethylene-2-ketone

An optically active, hydroxyheptane technology, which is applied in the field of preparation of optically active 7-halo-6-hydroxyhept-3-en-2-one, can solve the problems of harsh reaction conditions, high price, and high cost, and achieve the goal of preparing Simple, Wide-Source Effects

Active Publication Date: 2013-06-12
江西博雅欣和制药有限公司
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  • Abstract
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  • Claims
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Problems solved by technology

[0005] Evans et al (J. Am. Chem. Soc., 2012, 134, 2856-2859) reported a (I) Analog optically active 7-benzyloxy-6-hydroxyhept-3-en-2-one Preparation method: Under the catalysis of the second-generation Hoveyda-Grubbs catalyst, optically active 5-benzyloxy-4-hydroxyl-1 -Pentene and 3-buten-2-one are prepared by olefin metathesis reaction to prepare optically active 7-benzyloxy-6-hydroxyhept-3-en-2-one, but the second generation Hoveyda-Grubbs catalyst used in this method Expensive, difficult to recycle, harsh reaction conditions, need to operate in absolute anhydrous and oxygen-free operation, high cost, difficult to implement in large-scale production

Method used

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  • Preparation method of optically-active 7-halogenated-6-hydroxyheptane-3-ethylene-2-ketone
  • Preparation method of optically-active 7-halogenated-6-hydroxyheptane-3-ethylene-2-ketone
  • Preparation method of optically-active 7-halogenated-6-hydroxyheptane-3-ethylene-2-ketone

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Embodiment 1

[0027] Will( S )-5-Chloro-4-hydroxy-1-pentene (1.2 g) was dissolved in dichloromethane (25 ml), cooled to -40 °C with stirring, and ozone was introduced until the reaction solution turned blue ( for about 10 min), air was introduced until the blue color disappeared, a saturated aqueous solution of sodium thiosulfate (10 mL) was added, it was naturally raised to room temperature under stirring, extracted with dichloromethane, the organic layers were combined, dried over anhydrous sodium sulfate, and reduced Concentrate under pressure to get ( S )-4-Chloro-3-hydroxybutyraldehyde (1.13 g, 93%). The product was directly used in the next step reaction.

Embodiment 2

[0029] Will( R )-5-Chloro-4-hydroxy-1-pentene (1.2 g) was dissolved in dichloromethane (25 ml), cooled to -80 °C with stirring, and ozone was introduced until the reaction solution turned blue ( for about 10 min), air was introduced until the blue color disappeared, dimethyl sulfide (5 mL) was added, and it was naturally raised to room temperature under stirring, washed with saturated brine, the organic layer was dried over anhydrous sodium sulfate, and concentrated under reduced pressure. have to( R )-4-Chloro-3-hydroxybutyraldehyde (1.17 g, 96%). The product was directly used in the next step reaction.

Embodiment 3

[0031] Potassium tert-butoxide (0.6 g) was dissolved in tetrahydrofuran (20 mL), and 2-oxopropyl diethyl phosphate (1.0 g) was added dropwise with stirring at 0°C. add( S )-4-Chloro-3-hydroxybutyraldehyde (0.61 g) dissolved in tetrahydrofuran (5 mL) solution, after dropping, stir at room temperature for 10 h, after the reaction is complete, pour the reaction solution into saturated ammonium chloride solution, and use extracted with ethyl acetate, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain ( S )-7-Chloro-6-hydroxy-hept-3-en-2-one (0.80 g, 99%), =2.0 o ( c 0.94, CHCl 3 )

[0032] 1 H NMR (400MHz, CDCl 3 ): δ 6.79 (dt, 1H), 6.12 (d, 1H), 3.94 (m, 1H), 3.54 (dd, 1H), 3.48 (dd, 1H), 3.17 (br, 1H), 2.46 (m, 2H ), 2.21 (s, 3H).

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Abstract

The invention belongs to the technical field of organic chemistry, and particularly discloses a preparation method of optically-active 7-halogenated-6-hydroxyheptane-3-ethylene-2-ketone. The preparation method disclosed by the invention comprises the following steps of: preparing optically-active 4-halogenated-3-hydroxy-butyraldehyde via ozonization based on optically-active 5-halogenated-4-hydroxy-1-pentene as a raw material, and then reacting with 2-oxo-propyl phosphate Horner-Wadsworth-Emmons to prepare the optically-active 7-halogenated-6-hydroxyheptane-3-ethylene-2-ketone. The method is available in raw materials, moderate in conditions, simple and convenient to operate, and suitable for industrialized production.

Description

technical field [0001] The invention belongs to the technical field of organic chemistry, and in particular relates to a preparation method of optically active 7-halogenated-6-hydroxyhept-3-en-2-one. Background technique [0002] Optically active 7-halo-6-hydroxyhept-3-en-2-one (I) is an important pharmaceutical and chemical intermediate, which can be used in the asymmetric synthesis of statins, atorvastatin and rosuva Statins, etc. [0003] [0004] In the formula X is chlorine, bromine or iodine. C6 stereo configuration can be R -or S -structure. [0005] Evans et al. ( J. Am. Chem. Soc. , 2012 , 134, 2856-2859) reported a preparation method of an analogue of (I) optically active 7-benzyloxy-6-hydroxyhept-3-en-2-one: Catalyzed by the second generation Hoveyda-Grubbs catalyst , Optically active 7-benzyloxy-6-hydroxyhept-3-ene-2 ​​was prepared by olefin metathesis reaction of optically active 5-benzyloxy-4-hydroxy-1-pentene and 3-buten-2-one -ketone, but the secon...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C49/24C07C45/72
Inventor 陈芬儿熊方均李杰陈文学何秋琴
Owner 江西博雅欣和制药有限公司
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