3539-97-7

Usage

Uses

Used in Pharmaceutical Industry:
(S)-1,1,1-Trifluoro-2-propanol is used as an organic synthesis intermediate for the development of new pharmaceutical compounds. Its unique structure allows for the creation of a wide range of drugs with potential therapeutic applications, making it a crucial component in the drug discovery process.
Used in Agrichemical Industry:
In the agrichemical sector, (S)-1,1,1-Trifluoro-2-propanol is utilized as an intermediate for the synthesis of various agrochemicals, such as pesticides and herbicides. Its incorporation into these products can enhance their effectiveness and selectivity, leading to improved agricultural outcomes.
Used in Laboratory Research and Development:
(S)-1,1,1-Trifluoro-2-propanol is also employed in laboratory settings for research and development purposes. Its unique properties make it an attractive candidate for studying various chemical reactions and exploring new synthetic pathways, contributing to the advancement of scientific knowledge in the field.
Used in Chemical Production Processes:
Lastly, (S)-1,1,1-Trifluoro-2-propanol plays a vital role in chemical production processes, where it is used as an intermediate to synthesize a variety of compounds. Its versatility and reactivity make it a valuable asset in the chemical manufacturing industry, facilitating the production of numerous products with diverse applications.

Synthesis

A liquid medium was prepared to be composed of 2000 ml of an ion-exchanged water, 60 g of glucose, 30 g of peptone, 50 g of yeast extract, 4.8 g of potassium dihydrogenphosphate and 2.5 g of dipotassium hydrogen phosphate. The liquid medium was charged into a fermenter of 5 L capacity (available from B.E. MARUBISHI Co., Ltd. under the trade name of a MDN-type 5L(S)) and then subjected to steam sterilization at 121°C for 60 minutes. This liquid medium was inoculated with 80 ml of a suspension of Hansenula polymorpha NBRC0799, the suspension being obtained by conducting a preliminary culture on 100 ml of the same composition to be 2.0 × 109 cfu/ml. Then, it was cultured at 28°C, an air ventilation of 1 vvm and a stirring speed of 500 rpm for 24 hours, thereby preparing a suspension of 4.3 × 109 cfu/ml (or 86 g/L in terms of the weight of wet cell bodies). At this time, adjustment of pH was attained by using aqueous ammonia, so that a pH was adjusted at 6.5. After culture had terminated, the ventilation amount and the stirring speed were changed to 0.1 vvm and 50 rpm. A solution obtained by dissolving 125.2 g of 1,1,1-trifluoroacetone and 200 g of glucose in 300 ml of an ion-exchanged water prepared in another vessel was added to the suspension automatically by a computer program in the use of an online sugar concentration sensor (an online biosensor available from ABLE & Biott Co.,Ltd. under the trade name of BF-410), so as to maintain a glucose concentration of 2 %. It was confirmed that the yield obtained after a lapse of 168 hours was 94.9 % by monitoring the reduction of the substrate due to the microorganism every 24 hours, upon which the reaction was terminated.In order to recall 1,1,1-trifluoro-2-propanol produced from the reaction solution after termination of the reaction, distillation was performed. A distillate was recalled in an amount of 188 ml, from which it was found, by internal standard method of 19F-NMR, that 109.2 g of 1,1,1-trifluoro-2-propanol was contained. As a result of measuring the optical purity under the above-discussed analyzing conditions, the optical purity was confirmed to be 98.7% ee (S-configuration).

Upstream product

• 421-50-1 1,1,1-trifluoro-2-propanone 
• 359-41-1 1,1,1-trifluoro-2,3-epoxypropane 
• 130025-34-2 (S)-2-trifluoromethyl-oxirane 
• 67-56-1 methanol 
• 18454-30-3 (+)-3-(1-trifluoromethylethoxy)propionic acid 
• 143142-90-9 (2R)-2-(trifluoromethyl)oxirane 
• 88378-50-1 (S)-(+)-1-Bromo-3,3,3-trifluoro-2-propanol 
• 374-01-6 1,1,1-trifluoroisopropanol 

Downstream Products

• 845616-82-2 5-methane-sulfonyl-2-((S)-2,2,2-trifluoro-1-methyl-ethoxy)-benzoic acid 
• 1246442-51-2 carbonic acid 4-nitro-phenyl ester (S)-2,2,2-trifluoro-1-methyl-ethyl ester 
• 1252634-15-3 (2S,4R)-4-[2-Chloro-4-((S)-2,2,2-trifluoro-1-methyl-ethoxy)-benzenesulfonyl]-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl Ester 2-methyl Ester 
• 1364677-75-7 5-(4-chloro-3-(4-chloro-phenyl)-2-(S)-2,2,2-trifluoro-1-methyl-ethoxy)-pyridine 
• 1364677-63-3 6-(4-chloro-phenyl)-5-((S)-2,2,2-trifluoro-1-methyl-ethoxy)-pyrazine-2-carboxylic acid methyl ester 
• 1415818-02-8 (S)-1,1,1-trifluoropropan-2-yl 4-((1r,4r)-4-(3-cyanopyridin-4-yloxy)cyclohexyloxy)piperidine-1-carboxylate 
• 1434816-99-5 2-chloro-4-((S)-2,2,2-trifluoro-1-methylethoxy)-1-tritylsulfanyl benzene 
• 869569-63-1 C₁₀H₈ClF₃O₃ 

Relevant academic research and scientific papers

ION CHANNEL MODULATORS

The present invention is directed to, in part, fused heteroaryl compounds and compositions useful for preventing and/or treating a disease or condition relating to aberrant function of a voltage-gated, sodium ion channel, for example, abnormal late/persistent sodium current. Methods of treating a disease or condition relating to aberrant function of a sodium ion channel including neurological disorders (e.g., Dravet syndrome, epilepsy), pain, and neuromuscular disorders are also provided herein.

ION CHANNEL MODULATORS

Provided, in part, are compounds of Formula I pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof, which are useful in the treatment of conditions associated with the activity of sodium channels. Methods of treating a disease or condition relating to aberrant function of a sodium ion channel including neurological disorders (e.g., Dravet syndrome, epilepsy), pain, and neuromuscular disorders are also provided herein.

COMPOUNDS AND THEIR METHODS OF USE

The present invention is directed to, in part, fused heteroaryl compounds and compositions useful for preventing and/or treating a disease or condition relating to aberrant function of a voltage-gated, sodium ion channel, for example, abnormal late/persistent sodium current. Methods of treating a disease or condition relating to aberrant function of a sodium ion channel including Dravet syndrome or epilepsy are also provided herein.

COMPOUNDS AND THEIR METHODS OF USE

The present invention is directed to, in part, fused heteroaryl compounds and compositions useful for preventing and/or treating a disease or condition relating to aberrant function of a voltage-gated, sodium ion channel, for example, abnormal late/persistent sodium current. Methods of treating a disease or condition relating to aberrant function of a sodium ion channel including neurological disorders (e.g., Dravet syndrome, epilepsy), pain, and neuromuscular disorders are also provided herein.

ION CHANNEL MODULATORS

The present invention is directed to, in part, fused heteroaryl compounds and compositions useful for preventing and/or treating a disease or condition relating to aberrant function of a voltage-gated, sodium ion channel, for example, abnormal late/persistent sodium current. Methods of treating a disease or condition relating to aberrant function of a sodium ion channel including neurological disorders (e.g., Dravet syndrome, epilepsy), pain, and neuromuscular disorders are also provided herein.

Characterization of two carbonyl reductases from Ogataea polymorpha NBRC 0799

The enzyme responsible for the enantioselective production of (S)-1,1,1-trifluoro-2-propanol ((S)-TFP) from 1,1,1-trifluoroacetone (TFA) has been identified in Ogataea polymorpha NBRC 0799. We purified two carbonyl reductases, OpCRD-A and OpCRD-B from this strain, and revealed their characteristics. Both enzymes were specific to NADH, but the following characteristics were different: The molecular mass of subunit OpCRD-A was 40?kDa and that of OpCRD-B was 43?kDa. Amino acid sequences of both enzymes were only 21% identical. OpCRD-B contained 4?mol of zinc per mole of enzyme, but OpCRD-A did not. The optimal pH, temperature, pH stability, thermostability, and inhibitor specificity were also remarkably different. With regard to substrate specificity, both enzymes exhibited high reductase activity toward a wide variety of ketones, aldehydes and fluoroketones, and dehydrogenase activity toward 2-propanol and 2-butanol. The reductase activity was much higher than the dehydrogenase activity at acidic pH. OpCRD-A enantioselectively produced (S)-TFP from TFA, but OpCRD-B preferentially produced (R)-TFP. Thus, we concluded that OpCRD-A plays the main role in the production of (S)-TFP by a reaction of O. polymorpha NBRC 0799 cells and that OpCRD-A has great potential for efficient production of (S)-TFP, as it is an S-specific enzyme and does not catalyze the dehydrogenation of (S)-TFP.

Bitopertin synthetic method and intermediate

The present invention discloses a new synthesis method and intermediates of Bitopertin. According to the Bitopertin synthesis method, 5-methylsulfonyl-2-[(1S)-2,2,2-trifluoro-1-methylethoxy]benzoic acid is adopted as a raw material, and continuous multi-step operations such as chlorination, acylation, deprotection, condensation and re-crystallization are subjected to performed to obtain the Bitopertin, wherein the intermediates in each step do not require further purification, and the total yield can achieve more than or equal to 80%.

Trifluoro isopropyl-substituted taxol derivatives, and applications thereof

The invention relates to novel trifluoro isopropyl-substituted taxol derivatives. The trifluoro isopropyl-substituted taxol derivatives are compounds represented by formula I, and isomers, corresponding compounds, or pharmacologically acceptable salts of the compounds, wherein R is used for representing hydrogen atom, or C1-C4 straight-chain paraffins or branched chain paraffins, or C2-C4 straight-chain acyl or branched chain acyl. The invention also provides a preparation method of the trifluoro isopropyl-substituted taxol derivatives, and applications of the trifluoro isopropyl-substituted taxol derivatives in preparing antitumor drugs.

(S)-1,1,1-trifluoro-2-propanol synthesis method

The present invention discloses a (S)-1,1,1-trifluoro-2-propanol synthesis method, steps are as follows: hexane or cyclohexane solvent, 1,1,1-trifluoro-2-propanol and a catalyst are added into a Soxhlet extractor extraction flask, and the mass ratio of hexane or cyclohexane solvent to 1,1,1-trifluoro-2-propanol is 3-30: 1; Novozyme 435 is added into a Soxhlet extractor extraction tube; the upper portion of the Soxhlet extractor extraction tube is provided with a condenser for condensing reflux reaction for 10 to 24 hours; reactants in the Soxhlet extractor extraction flask are reacted under reflux conditions for 10 to 24 hours and cooled, then the catalyst is recovered by filtration, the hexane or cyclohexane solvent is recovered by concentration, a 10-20% sodium hydroxide or potassium hydroxide water solution is added for reaction for 5 to 10 hours and then rectification to obtain (S)-1,1,1-trifluoro-2-propanol. The raw materials are simple and easy to get, pollution is less during the reaction, the process is simple, complex equipment is not needed, the synthesis method is safe and reliable, the synthesis yield is high, a product with a high purity can be obtained after refining.

PHENYL-3-AZA-BICYCLO[3.1.0]HEX-3-YL-METHANONES AND THE USE THEREOF AS MEDICAMENT

The present inventions relates to substituted phenyl-3-aza-bicyclo[3.1.0]hex-3-yl-methanones of general formula (I) wherein R1, R2, R3, R4, R5 and R6 are as herein described or salts thereof, preferably pharmaceutically acceptable salts thereof. The invention further relates to the manufacture of said compounds, pharmaceutical compositions comprising a compound according to general formula (I), and the use of said compounds for the treatment of various conditions such as conditions concerning positive and negative symptoms of schizophrenia as well as cognitive impairments associated with schizophrenia, Alzheimers Disease and other neurological and psychiatric disorders. The compounds of the invention show glycine transporter-1 (GlyT 1) inhibiting properties.