154598-58-0

Basic information

• Product Name: (S)-2-(2-AMINO-5-CHLOROPHENYL)-4-CYCLOPROPYL-1,1,1-TRIFLUOROBUT-3-YN-2-OL
• Synonyms: (S)-2-(2-AMINO-5-CHLOROPHENYL)-4-CYCLOPROPYL-1,1,1-TRIFLUOROBUT-3-YN-2-OL
• CAS NO: 154598-58-0
• Molecular Weight: 0
• Mol File: 154598-58-0.mol

Chemical Properties

• Appearance: /
• CAS DataBase Reference: (S)-2-(2-AMINO-5-CHLOROPHENYL)-4-CYCLOPROPYL-1,1,1-TRIFLUOROBUT-3-YN-2-OL(CAS DataBase Reference)
• NIST Chemistry Reference: (S)-2-(2-AMINO-5-CHLOROPHENYL)-4-CYCLOPROPYL-1,1,1-TRIFLUOROBUT-3-YN-2-OL(154598-58-0)
• EPA Substance Registry System: (S)-2-(2-AMINO-5-CHLOROPHENYL)-4-CYCLOPROPYL-1,1,1-TRIFLUOROBUT-3-YN-2-OL(154598-58-0)

Safety Data

• Hazardous Substances Data: 154598-58-0(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Research:
(S)-2-(2-AMINO-5-CHLOROPHENYL)-4-CYCLOPROPYL-1,1,1-TRIFLUOROBUT-3-YN-2-OL is used as a key intermediate in the synthesis of pharmaceutical compounds for various therapeutic applications. Its unique structure and functional groups make it a promising candidate for the development of new drug candidates.
Used in Organic Synthesis:
In the field of organic synthesis, (S)-2-(2-AMINO-5-CHLOROPHENYL)-4-CYCLOPROPYL-1,1,1-TRIFLUOROBUT-3-YN-2-OL is used as a building block for the creation of complex organic molecules. Its fluorinated nature and unique functional groups can be exploited to synthesize a wide range of biologically active molecules.
Used in Medicinal Chemistry:
(S)-2-(2-AMINO-5-CHLOROPHENYL)-4-CYCLOPROPYL-1,1,1-TRIFLUOROBUT-3-YN-2-OL is used as a valuable building block in medicinal chemistry due to its stability and resistance to metabolic degradation. This property makes it an attractive candidate for the development of new drugs with improved pharmacokinetic profiles.
Used in Drug Discovery:
In the drug discovery process, (S)-2-(2-AMINO-5-CHLOROPHENYL)-4-CYCLOPROPYL-1,1,1-TRIFLUOROBUT-3-YN-2-OL is used as a starting material for the design and synthesis of novel therapeutic agents. Its unique structure and functional groups can be utilized to explore new chemical space and identify potential drug candidates with improved efficacy and safety profiles.
Used in Chemical Research:
(S)-2-(2-AMINO-5-CHLOROPHENYL)-4-CYCLOPROPYL-1,1,1-TRIFLUOROBUT-3-YN-2-OL is also used in chemical research to study the reactivity and properties of fluorinated alkyne compounds. This can lead to a better understanding of the fundamental chemistry of these types of molecules and potentially uncover new applications in various fields.

Upstream product

• 154598-53-5 1-(2-amino-5-chloro-phenyl)-2,2,2-trifluoro-ethanone 
• 201218-09-9 cyclopropyl acetylenyllithium 
• 75-89-8 2,2,2-trifluoroethanol 
• 6746-94-7 Cyclopropylacetylene 
• 195372-65-7 N-(2-bromo-4-chlorophenyl)pivalamide 
• 925-90-6 ethylmagnesium bromide 
• 220961-15-9 iodomagnesium cyclopropylacetylide 
• 216006-64-3 cyclopropylacetylene magnesium chloride 
• 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 
• 192935-82-3 2-cyclopropylethynyl-magnesium bromide 
• 181190-33-0 N-(4-chloro-2-(2,2,2-trifluoroacetyl)phenyl)pivalamide 
• 106-47-8 4-chloro-aniline 
• 65854-91-3 N-(4-chlorophenyl)-2,2-dimethylpropionamide 

Downstream Products

• 391860-73-4 6-chloro-2-cyclopropyl-4-(trifluoromethyl)quinoline 
• 1453095-83-4 3-bromo-6-chloro-2-cyclopropyl-4-(trifluoromethyl)quinoline 
• 1453095-77-6 3,6-dichloro-2-cyclopropyl-4-(trifluoromethyl)quinoline 
• 177530-94-8 (S)-N-(4-chloro-2-(4-cyclopropyl-1,1,1-trifluoro-2-hydroxybut-3-yn-2-yl)phenyl)pivalamide 

Relevant articles and documents

Oxidative removal of p-methoxybenzyl-amino protecting group in the presence of a proximal hydroxy function: A solution to a process problem in SUSTIVA (efavirenz) synthesis

A practical and scaleable synthetic procedure for the deprotection of a p-methoxy benzyl group from the tertiary carbinol 2 in the commercial synthesis of SUSTIVA (efavirenz) 1 is described. The methodology involves a two step, one pot operation with an isolated yield of 82.5% with a product purity of >99.5%.

A novel, highly enantioselective ketone alkynylation reaction mediated by chiral zinc aminoalkoxides

Kilogram-scale synthesis of the HIV reverse transcriptase inhibitor efavirenz was achieved by means of a highly enantioselective alkynylation of prochiral ketones 1 with alkynyllithium or alkynylmagnesium reagents in the presence of chiral zinc aminoalkoxides as mediators. With the achiral auxiliary 2,2,2-trifluoroethanol (R3=CF3CH2), the efavirenz precursor 2 (R1 =H, R2=cyclopropyl) was obtained with an ee of 99.2%.

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.