209414-27-7

Basic information

• Product Name: (S)-1-(2-Amino-5-chlorophenyl)-1-(trifluoromethyl)-3-cyclopropyl-2-propyn-1-ol
• Synonyms: BenzeneMethanol,2-aMino-5-chloro-a-(2-cyclopropylethynyl)-a-(trifluoroMethyl)-, (aS)-;(S)-1-(2-Amino-5-chlorophenyl)-1-(trifluoromethyl)-3-cyclopropyl-2-propyn-1-ol (E05);(2R)-2-(2-Amino-5-chlorophenyl)-4-cyclopropyl-1,1,1-trifluorobut-3-yn-2-ol;(R)-2-(2-Amino-5-chloro-phenyl)-4-cyclopropyl-1,1,1-trifluoro-but-3-yn-2-ol;(S)-5-Chloro-Alpha-(Cyclopropylethynyl)-2-Amino-Alpha-(Trifluoromethyl)-Benzenemethanol;(S)-1-(2-AMINO-5-CHLOROPHENYL)-1-(TRIFLUOROMETHYL)-3-CYCLOPROPYL-2-PROPYN-1-OL;(S)-5-CHLORO-A-(CYCLOPROPYLETHYNYL)-2-AMINO-A-(TRIFLUOROMETHYL)BENZENE METHANOL;Efavirenz Related Compound A (20 mg) ((S)-2-(2-amino-5-chlorophenyl)-4-cyclopropyl-1,1,1-trifluorobut-3-yn-2-ol)
• CAS NO: 209414-27-7
• Molecular Formula: C₁₃H₁₁ClF₃NO
• Molecular Weight: 289.68
• Mol File: 209414-27-7.mol

Chemical Properties

• Boiling Point: 425.052 °C at 760 mmHg
• Flash Point: 210.864 °C
• Appearance: /
• Density: 1.46
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.575
• Storage Temp.: 2-8°C(protect from light)
• Solubility: Chloroform (Slightly), DMSO (Slightly), Methanol (Slightly)
• PKA: 9.13±0.24(Predicted)
• CAS DataBase Reference: (S)-1-(2-Amino-5-chlorophenyl)-1-(trifluoromethyl)-3-cyclopropyl-2-propyn-1-ol(CAS DataBase Reference)
• NIST Chemistry Reference: (S)-1-(2-Amino-5-chlorophenyl)-1-(trifluoromethyl)-3-cyclopropyl-2-propyn-1-ol(209414-27-7)
• EPA Substance Registry System: (S)-1-(2-Amino-5-chlorophenyl)-1-(trifluoromethyl)-3-cyclopropyl-2-propyn-1-ol(209414-27-7)

Safety Data

• Hazardous Substances Data: 209414-27-7(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
(S)-1-(2-Amino-5-chlorophenyl)-1-(trifluoromethyl)-3-cyclopropyl-2-propyn-1-ol is used as an intermediate in the preparation of Efavirenz (E425000) impurity. Its role in the pharmaceutical industry is crucial for the development and synthesis of Efavirenz, which is an antiretroviral medication used to treat HIV/AIDS.
The compound's specific structural features allow it to serve as a key building block in the synthesis process, contributing to the overall effectiveness and potency of the final drug product. Its use in the pharmaceutical industry highlights the importance of complex organic compounds in the development of life-saving medications.

InChI:InChI=1/C13H11ClF3NO/c14-9-3-4-11(18)10(7-9)12(19,13(15,16)17)6-5-8-1-2-8/h3-4,7-8,19H,1-2,18H2/t12-/m0/s1

Upstream product

• 6746-94-7 Cyclopropylacetylene 
• 154598-53-5 1-(2-amino-5-chloro-phenyl)-2,2,2-trifluoro-ethanone 
• 192935-82-3 2-cyclopropylethynyl-magnesium bromide 
• 1576-35-8 toluene-4-sulfonic acid hydrazide 
• 209414-26-6 (S)-6-chloro-4-(cyclopropylethynyl)-2-(4-methoxyphenyl)-4-(trifluoromethyl)-1,4-dihydro-2H-benzo[d][1,3]oxazine 
• 221177-50-0 2-[5-chloro-2-(trityloamino)phenyl]-4-cyclopropyl-1,1,1-trifluorobut-3-yn-2-ol 
• 14267-92-6 1-chloro-4-pentyne 
• 1352784-88-3 1-(5-chloro-2-nitrophenyl)-3-cyclopropylprop-2-yn-1-ol 
• 1352784-89-4 1-(5-chloro-2-nitrophenyl)-3-cyclopropylprop-2-yn-1-one 
• 1352784-90-7 (S)-1-(5-chloro-2-nitrophenyl)-1-trifluoromethyl-3-cyclopropyl-2-propyn-1-ol 
• 75-89-8 2,2,2-trifluoroethanol 
• 195372-65-7 N-(2-bromo-4-chlorophenyl)pivalamide 
• 56571-91-6 (1R,2S)-1-phenyl-2-(1-pyrrolidinyl)-1-propanol 
• 201218-10-2 4-cyclopropyl-1,1,1-trifluoro-but-3-yn-2-one 

Downstream Products

• 154598-52-4 efavirenz 
• 211563-39-2 [4-Chloro-2-((S)-3-cyclopropyl-1-hydroxy-1-trifluoromethyl-prop-2-ynyl)-phenyl]-carbamic acid 4-nitro-phenyl ester 
• 211563-40-5 [4-Chloro-2-((S)-3-cyclopropyl-1-hydroxy-1-trifluoromethyl-prop-2-ynyl)-phenyl]-carbamic acid methyl ester 
• 391860-73-4 6-chloro-2-cyclopropyl-4-(trifluoromethyl)quinoline 
• 220978-02-9 (S)-5-chloro-α-(cyclopropylethynyl)-2-amino-α-(trifluoromethyl) benzenemethanol hydrocloride 
• 220978-05-2 (S)-2-[1-hydroxy-1-trifluoromethyl-3-cyclopropylpropyn-2-yl]-4-chloroaniline hydrobromide 
• 1236354-27-0 (S)-2-(2-amino-5-chlorophenyl)-4-cyclopropyl-1,1,1-trifluorobut-3-yn-2-ol methanesulfonate 
• 154801-74-8 (R)-efavirenz 
• 177530-94-8 (S)-N-(4-chloro-2-(4-cyclopropyl-1,1,1-trifluoro-2-hydroxybut-3-yn-2-yl)phenyl)pivalamide 
• 211563-41-6 C₁₆H₁₅ClF₃NO₃ 

Relevant articles and documents

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.

Method for asymmetric synthesis of anti-Aids drug, namely efavirenz key intermediate

The invention discloses a method for asymmetric synthesis of an anti-Aids drug, namely an efavirenz key intermediate. The method comprises the following steps that in an organic solvent, fluoride, anorganic ligand (9S)-6'-methoxy-deoxidized cinchonine-9-ol and cyclopropyl acetylene are evenly stirred, an organic zinc solution is slowly added at the temperature of 15-25 DEG C, after constant-temperature stirring is conducted for 3-5 hours, tetraisopropyl titanate is added, stirring is continued to be conducted for 2-3 hours, then the temperature is decreased to minus 20 DEG C to 0 DEG C, 5-chloro-2-amino-trifluorobenzophenone is added, a mixture is stirred at the temperature of minus 20 DEG C to 0 DEG C for 5-12 hours, after a reaction is completed, a proton source is added for a quenchingreaction, then a certain amount of activated carbon is added, a mixture is stirred for 0.5 hour and filtered, an organic phase and a water phase are separated in an extraction mode, the organic phaseis washed, dried and subjected to vacuum concentration, and after purification, the efavirenz key intermediate is obtained. The technological process is short, the technological condition is mild, operation is easy, environmental protection is achieved, the cost is low, and the method is suitable for industrial production.

Catalytic Enantioselective Synthesis of Key Propargylic Alcohol Intermediates of the Anti-HIV Drug Efavirenz

The catalytic, enantioselective synthesis of key propargylic alcohol intermediates toward the synthesis of the anti-HIV drug efavirenz is reported. Using a recently reported chiral-at-ruthenium catalyst (J. Am. Chem. Soc. 2017, 139, 4322), catalytic enantioselective alkynylations of 1-(2,5-dichlorophenyl)-2,2,2-trifluoroethanone (99% yield, 95% ee) and 1-(5-chloro-2-nitrophenyl)-2,2,2-trifluoroethanone (97% yield, 99% ee) are achieved using catalyst loadings of merely 0.2 mol % (ca. 500 TON).

Synthetic method of efavirenz key intermediate

The invention provides a synthetic method of an efavirenz key intermediate. The synthetic method comprises the following steps: carrying out reaction on parachloroaniline and pivaloyl chloride to protect amino to obtain N-(4-chlorphenyl)-2,2-dimethyl propanamide; carrying out Friedel-Crafts acylation reaction on the product and Friedel-Crafts acylation under action of aluminum trichloride to hydrolyze to obtain 4-chloro-2-trifluoroacetyl aniline hydrochloride in an acidic condition; and then carrying out alkalization to obtain 4-chloro-2-trifluoroacetyl aniline, carrying out reaction with cyclopropyl acetylene magnesium chloride in a catalytic system formed by a ligand (1R, 2S)-1-phenyl-2-(1-pyrrolidyl)-1-propyl alcohol, and carrying out an asymmetrical self-catalytic reaction to obtain the efavirenz key intermediate. The synthetic method of the efavirenz key intermediate, provided by the invention, is cheap and easily available in raw material, low in toxicity of reagent and mild in reaction condition, amino protection and deprotection are not carried out frequently, the line is concise, the yields of reaction of each step are excellent, and the total yield is high.

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.

Octahedral Ruthenium Complex with Exclusive Metal-Centered Chirality for Highly Effective Asymmetric Catalysis

A novel ruthenium catalyst is introduced which contains solely achiral ligands and acquires its chirality entirely from octahedral centrochirality. The configurationally stable catalyst is demonstrated to catalyze the alkynylation of trifluoromethyl ketones with very high enantioselectivity (up to >99% ee) at low catalyst loadings (down to 0.2 mol%).

Efavirenz intermediate synthesizing method

The invention relates to an efavirenz intermediate synthesizing method. The efavirenz intermediate synthesizing method comprises the following steps of: adding cyclopropyl acetylene magnesium bromide to a coordination compound prepared from neopentyl alcohol, a zinc salt or copper salt and (1R, 2S)-1-phenyl-2-(1-pyrrolidyl)-1-propyl alcohol by using 2-methyltetrahydrofuran as a solvent, reacting, adding 4-chlorine-2-(trifluoroacetyl) aniline, and carrying out heat-preservation stirring till ending; and transferring to a saturated citric acid solution for quenching, carrying out reduced pressure distillation after separating to obtain an organic phase, adding an polar organic solvent and L-amino acid after obtaining racemate, heating and mixing, carrying out cooling crystallization after resolution, and carrying out recrystallization after obtaining crystals to obtain white powder. Compared with the prior art, the efavirenz intermediate synthesizing method has the advantages that the 2-methyltetrahydrofuran which is a green solvent is used in reaction; the product with relatively high optical purity is obtained by using very few organic ligands; the yield is relatively high; the selectivity is good; the separation of products and the control of reaction conditions are easy; and the method conforms to green and environmental protection concept and is suitable for industrialized production.

Method for asymmetrically synthesizing key intermediate for efavirenz which is anti-AIDS (acquired immune deficiency syndrome) medicine

The invention discloses a method for asymmetrically synthesizing a key intermediate for efavirenz which is an anti-AIDS (acquired immune deficiency syndrome) medicine, and belongs to the field of technologies for synthesizing medicines. The method includes carrying out reaction on 2-methyltetrahydrofuran, alkaline reagents, alcohol compounds, chiral ammonia and alcohol solution and cyclopropyl acetylene; adding 5-chlorine-2-amino trifluorobenzene ketone into reaction products and carrying out addition reaction; terminating the reaction by the aid of reaction termination liquid to obtain the key intermediate which is (S)-2-amino-5-chlorine-alpha-cyclopropyl acetylene-alpha-benzotrifluoride benzyl alcohol for the efavirenz. The method has the advantages that required operation procedures for preparing lithium salt, sodium salt or Grignard reagents for cyclopropyl acetylene during industrial production can be omitted, accordingly, the operation difficulty of the reaction can be lowered to a great extent, the cost for the reaction can be reduced to a great extent, and the method is suitable for industrial production.

Preparation method of efavirenz intermediate

The invention relates to a preparation method of an efavirenz intermediate. The method comprises the following steps of reacting a zinc salt or copper salt with an organic ligand (1R, 2S)-1-phenyl-2-(1-pyrrolidyl)-1-propyl alcohol in an organic solvent, adding a cyclopropylene reagent; stirring at a constant temperature for 2h and adding 1-(5-chloro-2-nitrophenyl)-2,2,2-trifluoro-ethanone, completing stirring reaction, adding a proton source for quenching reaction and separating an organic phase from an aqueous phase through extraction; and adding an oil phase which is obtained through direct concentration and drying of the organic phase to a solution of tetrahydrofuran and methyl alcohol at a certain ratio, and then adding acetic acid and iron powder, stirring and filtering the obtained mixture through kieselguhr, washing, drying, carrying out vacuum concentration and purifying to obtain an efavirenz key intermediate. The 1-(5-chloro-2-nitrophenyl)-2,2,2-trifluoro-ethanone is utilized for participating in reaction, so that the method is short in process, mild in condition, simple in operation, green, environment-friendly and low in cost.

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.