Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Process for the synthesis of ethynylcyclopropane

A technology of ethynyl cyclopropane and alkyl group is applied in the synthesis field of ethynyl cyclopropane, which can solve the problems of low reaction temperature and achieve the effect of high yield

Inactive Publication Date: 2011-04-20
LONZA LTD +1
View PDF7 Cites 4 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The disadvantage of this method is that the preparation of harmonic dichlorides requires extremely stringent conditions (such as PCL 5 ), and for every equivalent of product produced, at least two equivalents of halide waste will have to be disposed of
Another disadvantage is that the reaction temperature in the mass production state is very low, only about -70°C to -100°C

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Process for the synthesis of ethynylcyclopropane
  • Process for the synthesis of ethynylcyclopropane
  • Process for the synthesis of ethynylcyclopropane

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0043] Example 1: (1,1-dimethoxy-ethyl)-cyclopropane (II)

[0044] At 25°C, add 82 grams (0.77 moles) of trimethyl orthoformate, 200 mL (4.94 moles) of methanol and 0.25 p-methylsulfonic acid to a flask containing 50 grams (0.59 moles) of cyclopropylmethyl ketone. g (1.45 mmol). The resulting solution was stirred at 25°C for 2 hours. 0.15 g (2.78 mmol) of sodium methoxide was added to the solution under vigorous stirring. Methyl formate, methanol and trimethyl orthoformate were removed under reduced pressure (approximately 250-300 mbar). The residue was washed with 100 ml of brine and dried over 15 g of sodium sulfate. Finally, a colorless liquid of (1,1-dimethoxyethyl)cyclopropane with a concentration of 45-65% is obtained.

Embodiment 2

[0045] Example 2: (1-Cyclopropylvinylsulfanyl)-Benzene (IV)

[0046] Add 1.3 grams (0.10 moles) of (1,1-dimethoxyethyl) cyclopropane, 11 grams (0.10 moles) of thiophenol, 250 milliliters of toluene and 700 grams (3 mmoles) of 10-camphorsulfonic acid In a flask with a funnel attached. The pressure-balanced dropping funnel was equipped with molecular sieves (beads) and a reflux condenser was installed at the top. The solution was refluxed at 130°C (bath temperature) for 20 hours. The mixture was washed with 10% aqueous NaOH (2 x 50 mL) and brine, and dried over 5 g of sodium sulfate. The toluene was removed under reduced pressure to yield an oil containing 46% (1-cyclopropylvinylsulfanyl)benzene. The crude product can be further purified, eg by distillation.

Embodiment 3

[0047] Embodiment 3: Ethynyl cyclopropane (I)

[0048] KAPA (potassium aminopropylamide) is either generated in situ from potassium hydride and 1,3-diaminopropane (Brown, C.A.J., Org. Chem. 1978.43.3083-3084), or in the presence of Fe(NO 3 ) 3 Generated in situ from potassium and 1,3-diaminopropane (Kimmel, T et al. Org. Chem. 1984, 49.2494-2496) in the presence of a catalyst. 358 mg (2.03 mmol) of (1-cyclopropylvinyl) sulfanylbenzene was added dropwise to a flask containing a newly generated KAPA solution (10 ml at 1,3 - in diaminopropane, concentration 1.27 mol / L, 12.7 mmol). The mixture was stirred at 25°C for 3 hours, then cooled to 0°C. Add ice water to the mixture. The yield of ethynylcyclopropane in the raw product was 88%. The mixture was washed with 2 x 50 mL of AcOH aqueous solution and 100 mL of brine, and washed with 2 g of Na 2 SO 4 dry. The raw product is purified by distillation. The boiling point is: 50-51°C.

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

Ethynylcyclopropane is prepared in a two-step process by reacting (1,1-dimethoxyethyl)- cyclopropane with a thiol and eliminating the thiol from the intermediate.

Description

technical field [0001] The present invention relates to formula [0002] [0003] A two-step method for the preparation of ethynylcyclopropane, which is an intermediate in the synthesis of active pharmaceutical ingredients such as antiviral agents: (-) 6-chloro-4-cyclopropylacetylene Base-4-trifluoromethyl-1,4-dihydro-2H-3,1-benzoxazin-2-one, which is a highly effective human immunodeficiency antiviral (HIV) reverse transcriptase inhibitor (WO-A96 / 22955). Background technique [0004] The synthesis method of the compound of formula I disclosed in US-B-6552239 starts from cyclopropanaldehyde and diazophosphonate. This reaction is also known as Seyferth-Gilbert alkyne synthesis. Cyclopropanaldehyde is obtained by removing two molecules of hydrogen chloride from (1,1-dichloroethyl) cyclopropane. The disadvantage of this method is that the preparation of harmonic dichlorides requires extremely stringent conditions (such as PCL 5 ), and for every equivalent of product pro...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
IPC IPC(8): C07C1/20C07C13/04
CPCC07C319/14C07C1/322C07C2101/02C07C13/04C07C2531/02C07C2601/02C07C321/28
Inventor 保罗·汉塞尔曼黄希蓝陈彦磊
Owner LONZA LTD
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com