154635-17-3

Usage

InChI:InChI=1/C14H9ClF3NO2/c15-9-3-4-11-10(7-9)13(14(16,17)18,21-12(20)19-11)6-5-8-1-2-8/h3-4,7-8H,1-2H2,(H,19,20)

Upstream product

• 181377-64-0 (S)-6-Chloro-4-cyclopropylethynyl-4-trifluoromethyl-1-((1S,4R)-4,7,7-trimethyl-3-oxo-2-oxa-bicyclo[2.2.1]heptane-1-carbonyl)-1,4-dihydro-benzo[d][1,3]oxazin-2-one 
• 106-47-8 4-chloro-aniline 
• 173676-60-3 (S)-5-chloro-α-(cyclopropylethynyl)-2-<<(4-methoxyphenyl)methyl>amino>-α-(trifluoromethyl)benzenemethanol 
• 209414-27-7 (2S)-2-(2-amino-5-chlorophenyl)-4-cyclopropyl-1,1,1-trifluorobut-3-yn-2-ol 
• 503-38-8 trichloromethyl chloroformate 
• 106-46-7 para-dichlorobenzene 
• 1381993-88-9 (S)-2-(2,5-dichlorophenyl)-4-cyclopropyl-1,1,1-trifluorobut-3-yn-2-ol 
• 1381993-90-3 (S)-carbamic acid cyclopropyl-(2,5-dichloro-phenyl)-trifluoromethyl-prop-2-ynyl ester 
• 886371-22-8 1-(2,5-dichloro-phenyl)-2,2,2-trifluoroethanone 
• 177530-93-7 rac-efavirenz 
• 105-58-8 Diethyl carbonate 
• 18437-66-6 N-(t-butoxycarbonyl)-4-chloroaniline 
• 201218-07-7 tert-butyl-4-chloro-2-(2,2,2-trifluoroacetyl)phenyl carbamate 
• 6746-94-7 Cyclopropylacetylene 

Downstream Products

• 205754-33-2 8-Hydroxyefavirenz 

Relevant academic research and scientific papers

Efavirenz synthesis method and method for preparing intermediate of efavirenz

The invention discloses an efavirenz synthesis method and a method for preparing an intermediate of efavirenz. The efavirenz synthesis method comprises the following steps: mixing (2S)-2-(2-amino-5-chlorphenyl)-4-cyclopropyl-1, 1, 1-trifluoromethyl-3-butyne-2-ol, methyl tert-butyl ether and a potassium bicarbonate aqueous solution; adding a triphosgene-containing benzene or triphosgene-containingisopropyl ether solution, and reacting until the raw materials disappear; separating liquid, and washing with edible salt water; drying and concentrating the organic phase to obtain a crude product efavirenz; and recrystallizing to obtain the efavirenz. The yield of the product is improved, so that the cost is greatly reduced, and the market competitiveness is improved.

Development and Validation of RP-Chiral HPLC Method for Determination of (R)-Enantiomer Excess Content in Efavirenz

A simple, specific, linear, accurate and precise reverse phase chiral HPLC method was developed for the separation of efavirenz enantiomers by using the Lux Amylose-2 column containing amylose tris(5-chloro-2-methyl phenyl carbamate) as a stationary phase. The mobile phase consists of 0.1 % formic acid in water and acetonitrile (55:45, v/v). The flow rate was kept at 1.0 mL/min and the detection wavelength used 252 nm and the column temperature was set at 25 oC. The limit of detection was 0.01 mg/mL and the limit of quantification was 0.04 mg/mL. The linearity calibration curve of (R)-enantiomer was shown well from the range of 0.04 mg/mL to 0.4 mg/mL. The values of the correlation coefficient were 0.999 and 0.999 for (R)-enantiomer and (S)-efavirenz, respectively. The percentage recoveries of (R)-enantiomer from efavirenz drug substance were ranged from 93.5% to 107.5%. The results demonstrated that developed RP-chiral HPLC method was simple, precise, robust and applicable for the estimation of (R)-enantiomer in efavirenz API. This method was validated in as per ICH Q2 (R1) and USP validation of compendial methods .

METHOD FOR THE MANUFACTURE OF EFAVIRENZ

This invention relates to a method for the manufacture of optically pure (S)-6- chloro-(cyclopropylethynyl)-1,4-dihydro-4-(trifluoromethyl)-2H-3,1 -benzoxazin- 2-one. Specifically, this invention relates to a flow synthesis method for the manufacture of (S)-6-chloro-(cyclopropylethynyl)-1,4-dihydro-4- (trifluoromethyl)-2H-3,1 -benzoxazin-2-one.

Alkynyl Cinchona Catalysts affect Enantioselective Trifluoromethylation for Efavirenz under Metal-Free Conditions

Efavirenz is manufactured worldwide, and its asymmetric synthesis requires a complex organometallic approach, while an organocatalytic approach is far less efficient. The first highly enantioselective approach is disclosed for the synthesis of Efavirenz under nonmetal organocatalysis with up to 93% ee for the Merck intermediate and 91% ee for the Lonsa intermediate using novel alkynyl cinchona catalysts.

waylen apperception HIV reverse transcriptase inhibitors in accordance with the law of the process for the asymmetric synthesis of one-pot synthesis (by machine translation)

The invention relates to a novel one pot method asymmetric synthesis process of a (S)-6-chlorine-4-cylopropyl ethylnen-4-trifluoromethyl-1,4-dihydro-2H-1,3-benzoxazine-2-ketone (Efavirenz) compound, the compound can be used as an reverse transcriptase inhibitor for human immunodeficiency virus (HIV). The invention also relates to a novel aminoalcohol ligand used for the process.

Eluent tolerance and enantioseparation recovery of chiral packing materials based on chitosan bis(phenylcarbamate)-(n-octyl urea)s for high performance liquid chromatography

The goal of the present work was to study the influence of the swelling of chitosan derivatives on the enantioseparation and the separation performance recovery of chiral stationary phases (CSPs) based on these derivatives. Therefore, six chitosan bis(phenylcarbamate)-(n-octyl urea)s were synthesized, which were coated on macroporous 3-aminopropyl silica gel affording new CSPs. Most of the CSPs demonstrated strong enantioseparation capability for the tested chiral compounds. The swelling capacity of the chitosan bis(phenylcarbamate)-(n-octyl urea)s in ethyl acetate, acetone and tetrahydrofuran (THF) was evaluated. Among the chitosan derivatives, the chitosan bis(3,5-dichlorophenylcarbamate)-(n-octyl urea) polymer showed the highest swelling capacity in ethyl acetate and THF. The polymer-based CSPs could be utilized with pure ethyl acetate and a normal phase containing 70% THF, but was damaged by pure THF. On the other hand, the separation performance of the damaged CSP could be recovered after it was allowed to stand for a period of time. The observations are important for the development and application of polysaccharide derivative-based CSPs.

Synthesis method of chiral cyclopropylacetylenyl tert-alcohol compound

The invention provides a synthesis method of chiral cyclopropylacetylenyl tert-alcohol compound. The optically active propynol compound is obtained through a reaction of chiral amine alcohol or chiral aminodiol as a ligand in the presence of an alkaline regent and salt. The method concretely comprises the following steps: 1, reacting cyclopropyl acetylene with a chiral induction reagent, a chiral auxiliary reagent and zinc halide in an organic solvent in the presence of an alkaline reagent and sulfonate or sulfinate to obtain a first reaction mixture; and 2, reacting the first reaction mixture with 5-chloro-2-aminotrifluorobenzophenone to form (S)-2-amino-5-chloro-alpha-cyclopropylacetylenyl-alpha-trifluoromethylbenzyl alcohol. The method avoids use of an organic zinc reagent and a Grignard reagent, has the advantages of safe production, environmentally-friendly route, low production cost, and high yield and high chiral ee value of the obtained product, and is suitable for industrial production.

PROCESS FOR THE PREPARATION OF EFAVIRENZ USING KETON SOLVENTS

Object of the present invention is an improved process for the preparation of Efavirenz, avoiding the distillations of the solvents.

AN IMPROVED PROCESS FOR THE PREPARATION OF A NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITOR

The present invention relates to an improved process for the preparation of a non-nucleoside reverse transcriptase inhibitor. Specifically, the present invention relates to an improved process for the preparation of Efavirenz of Formula 1. The present invention also relates to a process for the preparation of compound of Formula 2, an intermediate used in the preparation of Efavirenz, wherein X is a halogen atom; X1 is a leaving group.

PROCESS FOR THE SYNTHESIS OF CHIRAL PROPARGYLIC ALCOHOLS

A process for the synthesis of chiral propargylic alcohols.