585-50-2

Usage

Uses

Used in Chemical Industry:
3-(3-Trifluoromethylphenyl)propionic acid is used as a catalyst for facilitating various chemical reactions. Its unique structure allows it to participate in different reaction mechanisms, enhancing the efficiency and selectivity of the processes it is involved in.
Used in Pharmaceutical Industry:
3-(3-Trifluoromethylphenyl)propionic acid is also utilized in the development of pharmaceutical compounds. Its chemical properties make it a valuable building block for the synthesis of new drugs, particularly those targeting specific biological pathways.
Used in Material Science:
In the field of material science, 3-(3-Trifluoromethylphenyl)propionic acid can be employed as a component in the development of new materials with specific properties. Its unique structure can contribute to the creation of materials with enhanced performance characteristics, such as improved stability or reactivity.

InChI:InChI=1/C10H9F3O2/c11-10(12,13)8-3-1-2-7(6-8)4-5-9(14)15/h1-3,6H,4-5H2,(H,14,15)

Synthetic route

3-(trifluoromethyl)cinnamic acid (779-89-5) → 3-(3-trifluoromethylphenyl)propanoic acid (585-50-2)

Conditions	Yield
With hydrogen; palladium dihydroxide at 40 - 60℃; under 2250.23 Torr;	100%
With palladium on activated charcoal; hydrogen; sodium carbonate In water at 25℃; under 1500.15 - 2250.23 Torr; for 3h;	99.4%
With hydrogen; palladium on activated charcoal In methanol at 20 - 25℃; under 30.003 Torr;	95.2%

3-(trifluoromethyl)cinnamic acid (779-89-5) → 3-(3-trifluoromethylphenyl)propanoic acid (585-50-2)

Conditions	Yield
With hydrogen; 5% Pd(II)/C(eggshell) In methanol at 25℃; under 735.572 Torr; for 10h;	100%
Stage #1: 3-(trifluoromethyl)cinnamic acid With palladium diacetate; 4,4,5,5-tetramethyl-[1,3,2]-dioxaboralane In dichloromethane at 25℃; for 12h; Schlenk technique; Inert atmosphere; Stage #2: With hydrogenchloride In water	97%
With palladium diacetate; 4,4,5,5-tetramethyl-[1,3,2]-dioxaboralane In dichloromethane at 25℃; for 12h; Sealed tube; Inert atmosphere; chemoselective reaction;	97%

3-(3-(trifluoromethyl)phenyl)propanenitrile (95096-06-3) → 3-(3-trifluoromethylphenyl)propanoic acid (585-50-2)

Conditions	Yield
With hydrogenchloride; water for 4.5h; Product distribution / selectivity;	94%
With sodium hydroxide; water In ethylene glycol at 125℃; for 9h; Product distribution / selectivity;

2-vinyl-1,3-dioxolane (3984-22-3) + 3-bromo-1-trifluoromethylbenzene (401-78-5) → 3-(3-trifluoromethylphenyl)propanoic acid (585-50-2)

Conditions	Yield
Stage #1: 2-vinyl-1,3-dioxolane; 3-bromo-1-trifluoromethylbenzene With potassium carbonate; Pd-Tedicyp catalyst In N,N-dimethyl-formamide at 110℃; for 20h; Heck reaction; Stage #2: With sodium hydroxide; water In N,N-dimethyl-formamide at 50 - 80℃;	93%

(E)-2-Oxo-4-(3-trifluoromethyl-phenyl)-but-3-enoic acid → 3-(3-trifluoromethylphenyl)propanoic acid (585-50-2) + (E)-3-(3-(trifluoromethyl)phenyl)acrylaldehyde (262268-58-6)

Conditions	Yield
With edetate disodium; thiamine diphosphate; sodium citrate; magnesium chloride In water; acetonitrile at 20℃; Rate constant; pH 6.0, brewers' yeast pyruvate decarboxylase (PDC, EC 4.1.1.1), also in the presence of pyruvamide;

3-<2-chloro-ethyl>-trifluoromethyl-benzene → 3-(3-trifluoromethylphenyl)propanoic acid (585-50-2)

Conditions	Yield
With carbon dioxide; magnesium

m-trifluoromethyl-α-chlorohydrocinnamic acid → 3-(3-trifluoromethylphenyl)propanoic acid (585-50-2)

Conditions	Yield
Stage #1: m-trifluoromethyl-α-chlorohydrocinnamic acid With acetic acid; zinc In water at 20 - 35℃; for 1h; Stage #2: With hydrogenchloride In water at 20℃; Product distribution / selectivity;

methyl 3-(3-(trifluoromethyl)phenyl)propanoate (294856-02-3) → 3-(3-trifluoromethylphenyl)propanoic acid (585-50-2)

Conditions	Yield
Stage #1: methyl 3-(3-(trifluoromethyl)phenyl)propanoate With sodium hydroxide; isopropyl alcohol at 20℃; for 6h; Stage #2: With hydrogenchloride; water
Stage #1: methyl 3-(3-(trifluoromethyl)phenyl)propanoate With lithium hydroxide monohydrate In tetrahydrofuran; water at 20℃; for 48h; Stage #2: With hydrogenchloride In tetrahydrofuran; diethyl ether; water
With water; sodium hydroxide In methanol at 20℃; for 4h;	3.9 g

3-Trifluoromethylbenzaldehyde (454-89-7) → 3-(3-trifluoromethylphenyl)propanoic acid (585-50-2)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: piperidine / pyridine / 50 - 75 °C / Inert atmosphere 1.2: 0 °C / Cooling with ice 2.1: hydrogen / palladium 10% on activated carbon / methanol / 2.5 h / 750.08 Torr View Scheme
Multi-step reaction with 2 steps 1.1: pyridine; piperidine / 4.25 h / 20 - 120 °C / Inert atmosphere 1.2: pH 2 2.1: sodium hydroxide / water / 20 °C 2.2: 7 h / 25 - 30 °C / 750.08 Torr 2.3: pH 2 View Scheme

3-bromo-1-trifluoromethylbenzene (401-78-5) → 3-(3-trifluoromethylphenyl)propanoic acid (585-50-2)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: palladium diacetate; potassium carbonate; triphenylphosphine / N,N-dimethyl-formamide / 15 h / 110 °C / Inert atmosphere 1.2: 15 h / 20 °C / 760.05 Torr 2.1: lithium hydroxide monohydrate / tetrahydrofuran; water / 48 h / 20 °C View Scheme

3-Trifluoromethylbenzyl chloride (705-29-3) → 3-(3-trifluoromethylphenyl)propanoic acid (585-50-2)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: sodium hydride / tetrahydrofuran / 0.5 h / 0 - 5 °C 1.2: 2 h 2.1: sodium chloride / water; N,N-dimethyl-formamide / 6 h / 150 °C 3.1: sodium hydroxide; water / methanol / 4 h / 20 °C View Scheme

dimethyl 2-(3-(trifluoromethyl)benzyl)malonate → 3-(3-trifluoromethylphenyl)propanoic acid (585-50-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium chloride / water; N,N-dimethyl-formamide / 6 h / 150 °C 2: sodium hydroxide; water / methanol / 4 h / 20 °C View Scheme

methanol (67-56-1) + 3-(3-trifluoromethylphenyl)propanoic acid (585-50-2) → methyl 3-(3-(trifluoromethyl)phenyl)propanoate (294856-02-3)

Conditions	Yield
With sulfuric acid Reflux;	99%
With thionyl chloride for 4h; Inert atmosphere; Reflux;	97%
With sulfuric acid at 30 - 45℃;

2-Amino-5-(4-methyl-phenyl)-thiophene-3-carboxylic Acid Amide + 3-(3-trifluoromethylphenyl)propanoic acid (585-50-2) → C22H17F3N2OS (1393911-92-6)

Conditions	Yield
With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine In chloroform at 120℃; Microwave irradiation;	98%

3-(3-trifluoromethylphenyl)propanoic acid (585-50-2) + (R)-<1-(1-Naphthyl)ethyl>ammonium chloride (82572-04-1) → (R)‐N‐(1‐(naphthalen‐1‐yl)ethyl)‐3‐(3‐trifluoromethylphenyl)propanamide (1005450-55-4)

Conditions	Yield
Stage #1: (R)-<1-(1-Naphthyl)ethyl>ammonium chloride With sodium hydroxide In toluene Stage #2: 3-(3-trifluoromethylphenyl)propanoic acid In toluene at 140 - 150℃; Further stages.;	95%

3-(3-trifluoromethylphenyl)propanoic acid (585-50-2) → 3-[3-(trifluoromethyl)phenyl]propan-1-ol (78573-45-2)

Conditions	Yield
Stage #1: 3-(3-trifluoromethylphenyl)propanoic acid With borane-THF In tetrahydrofuran at 0 - 20℃; for 25h; Stage #2: With water In tetrahydrofuran; methanol	94%
With borane In tetrahydrofuran at 0 - 20℃; for 25h; Inert atmosphere;	94%
Stage #1: 3-(3-trifluoromethylphenyl)propanoic acid With 4-methyl-morpholine; chloroformic acid ethyl ester In 2-methyltetrahydrofuran at -10 - -5℃; for 0.00166667h; Stage #2: With sodium tetrahydroborate In 2-methyltetrahydrofuran; water at 0 - 5℃; for 0.5h; Solvent; Reagent/catalyst;	92.2%

3-(3-trifluoromethylphenyl)propanoic acid (585-50-2) → 3-(trifluoromethyl)benzenepropanoic acid chloride (455-03-8)

Conditions	Yield
With thionyl chloride; N,N-dimethyl-formamide In Isopropyl acetate at 43℃; Temperature;	93%
With thionyl chloride
With thionyl chloride In toluene for 2h; Heating;

(R)-1-(1-Naphthyl)ethylamine (3886-70-2) + 3-(3-trifluoromethylphenyl)propanoic acid (585-50-2) → cinacalcet (226256-56-0)

Conditions	Yield
With tris(pentafluorophenyl)borate; phenylsilane In dibutyl ether at 120℃; for 24h; Solvent; Reagent/catalyst; Concentration; Inert atmosphere; Schlenk technique;	89%
With tris(pentafluorophenyl)borate; phenylsilane In dibutyl ether at 120℃; for 20h; Schlenk technique; Inert atmosphere;	87%
With potassium phosphate; 18-crown-6 ether; phenylsilane In tetrahydrofuran at 80℃; for 36h; Glovebox; Molecular sieve; Schlenk technique;

(S)-2-(p-tolylsulfinyl)aniline + 3-(3-trifluoromethylphenyl)propanoic acid (585-50-2) → (S)-3-(3-trifluoromethylphenyl)-N-(2-(p-tolylsulfinyl)phenyl)propanamide

Conditions	Yield
With dmap; 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine In N,N-dimethyl-formamide at 20℃; for 16h;	86%

(R)-1-(1-Naphthyl)ethylamine (3886-70-2) + 3-(3-trifluoromethylphenyl)propanoic acid (585-50-2) → (R)‐N‐(1‐(naphthalen‐1‐yl)ethyl)‐3‐(3‐trifluoromethylphenyl)propanamide (1005450-55-4)

Conditions	Yield
With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 15h; Inert atmosphere;	83%
Stage #1: 3-(3-trifluoromethylphenyl)propanoic acid With 1,1'-carbonyldiimidazole In dichloromethane for 1h; Stage #2: (R)-1-(1-Naphthyl)ethylamine In dichloromethane at 25 - 35℃; Solvent; Temperature;	82.94%
Stage #1: 3-(3-trifluoromethylphenyl)propanoic acid With thionyl chloride; N,N-dimethyl-formamide In toluene at 25 - 75℃; for 2h; Stage #2: (R)-1-(1-Naphthyl)ethylamine With triethylamine In dichloromethane; toluene at 0 - 5℃; for 1.5 - 2h;	70.87%

3-(3-trifluoromethylphenyl)propanoic acid (585-50-2) + diisopropylamine (108-18-9) → C16H22F3NO

Conditions	Yield
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 12h;	79%

3-(3-trifluoromethylphenyl)propanoic acid (585-50-2) → 3-[3-(trifluoromethyl)phenyl]propanal (21172-41-8)

Conditions	Yield
With succinic acid anhydride; 4,4'-dibromo-2,2'-bipyridine; diphenylsilane; nickel(II) hydroxide In tetrahydrofuran at 70℃; for 10h; Schlenk technique; Inert atmosphere;	75%
Multi-step reaction with 2 steps 1: 85 percent / LAH 2: 65 percent / (COCl)2/DMSO; Et3N View Scheme
Multi-step reaction with 2 steps 1.1: sulfuric acid / 30 - 45 °C 2.1: diisobutylaluminium hydride / toluene; hexane / 2.5 h / -80 - -78 °C 2.2: -80 - -78 °C View Scheme
Multi-step reaction with 2 steps 1: lithium aluminium tetrahydride / tetrahydrofuran / 0 - 20 °C / Inert atmosphere; Schlenk technique 2: Dess-Martin periodane / tetrahydrofuran / 2 h / 20 °C / Inert atmosphere; Schlenk technique View Scheme
Multi-step reaction with 2 steps 1: lithium aluminium tetrahydride / tetrahydrofuran / 0 - 20 °C / Inert atmosphere 2: Dess-Martin periodane / dichloromethane / 0 - 20 °C / Inert atmosphere View Scheme

(R)-1-(1-Naphthyl)ethylamine (3886-70-2) + 3-(3-trifluoromethylphenyl)propanoic acid (585-50-2) → cinacalcet hydrochloride (364782-34-3)

Conditions	Yield
Stage #1: (R)-1-(1-Naphthyl)ethylamine; 3-(3-trifluoromethylphenyl)propanoic acid With platinum(0)-1,3-divinyl-1,1,3,3-tetramethyldisiloxane complex; phenylsilane; 1,2-bis-(diphenylphosphino)ethane In dibutyl ether at 120℃; for 18h; Schlenk technique; Inert atmosphere; Stage #2: With hydrogenchloride In diethyl ether at -20℃; Schlenk technique; Inert atmosphere;	74%

2-methyl-1H-indole (95-20-5) + 3-(3-trifluoromethylphenyl)propanoic acid (585-50-2) → C19H18F3N

Conditions	Yield
With aluminium(III) triflate; Co(acac)3; hydrogen; [2-((diphenylphospino)methyl)-2-methyl-1,3-propanediyl]bis[diphenylphosphine] at 140℃; under 22502.3 Torr; for 18h; Autoclave; Sealed tube;	72%

3-(3-trifluoromethylphenyl)propanoic acid (585-50-2) + aniline (62-53-3) → N-(3-(3-(trifluoromethyl)phenyl)propyl)aniline

Conditions	Yield
With cobalt(II) tetrafluoroborate hexahydrate; (p-anisyl)triphos; hydrogen In 1,4-dioxane at 140℃; under 30003 Torr; for 24h; Autoclave; Green chemistry;	69%

Succinimide (123-56-8) + 3-(3-trifluoromethylphenyl)propanoic acid (585-50-2) → 3-(3-trifluoromethylphenyl)propanoyl succinimide

Conditions	Yield
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane for 18h; Inert atmosphere;	53%
Stage #1: 3-(3-trifluoromethylphenyl)propanoic acid With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In tetrahydrofuran for 0.5h; Inert atmosphere; Stage #2: Succinimide In tetrahydrofuran for 48h;	44%

3-(3-trifluoromethylphenyl)propanoic acid (585-50-2) + N-(6-(3-amino-4-fluorophenoxy)benzo[d]thiazol-2-yl)cyclopropanecarboxamide → N-(6-(4-fluoro-3-(3-(3-(trifluoromethyl)phenyl)propionylamino)phenoxy)benzo[d]thiazol-2-yl)cyclopropanecarboxamide

Conditions	Yield
With HATU In pyridine at 85℃; for 8h; Inert atmosphere;	39%

2-amino-1-(1-phenyl-3,4-dihydropyrrolo[1,2-a]pyrazin-2(1H)-yl)ethanone (1020656-57-8) + 3-(3-trifluoromethylphenyl)propanoic acid (585-50-2) → N-(2-oxo-2-(1-phenyl-3,4-dihydropyrrolo[1,2-a]pyrazin-2-yl)ethyl)-3-(3-(trifluoromethyl)phenyl)propanamide (1020656-11-4)

Conditions	Yield
Stage #1: 3-(3-trifluoromethylphenyl)propanoic acid With 1,1'-carbonyldiimidazole In dichloromethane at 20℃; for 1h; Stage #2: 2-amino-1-(1-phenyl-3,4-dihydropyrrolo[1,2-a]pyrazin-2(1H)-yl)ethanone In dichloromethane at 20℃; for 16h;	38%

3-(3-trifluoromethylphenyl)propanoic acid (585-50-2) → 3-[3-(trifluoromethyl)cyclohexyl]propanoic acid (329-02-2)

Conditions	Yield
With acetic acid; platinum Hydrogenation;

3-(3-trifluoromethylphenyl)propanoic acid (585-50-2) + diazomethyl-trimethyl-silane (18107-18-1) → methyl 3-(3-(trifluoromethyl)phenyl)propanoate (294856-02-3)

Conditions	Yield
With methanol Esterification;

4-{2-[(1S)-((S)-tert-butanesulfinylamino)-3-methylbutyl]-4-(trifluoromethyl)phenyl}-1-piperazine (851484-80-5) + 3-(3-trifluoromethylphenyl)propanoic acid (585-50-2) → 2-Methyl-propane-2-sulfinic acid [(S)-3-methyl-1-(5-trifluoromethyl-2-{4-[3-(3-trifluoromethyl-phenyl)-propionyl]-piperazin-1-yl}-phenyl)-butyl]-amide

Conditions	Yield
With N-(3-dimethylaminopropyl)-N-ethylcarbodiimide In dichloromethane; N,N-dimethyl-formamide

3-(3-trifluoromethylphenyl)propanoic acid (585-50-2) → [(S)-1-(7,8-Dihydro-naphthalen-1-yl)-ethyl]-[3-(3-trifluoromethyl-phenyl)-propyl]-amine

Conditions	Yield
Multi-step reaction with 3 steps 1: 85 percent / LAH 2: 65 percent / (COCl)2/DMSO; Et3N View Scheme

3-(3-trifluoromethylphenyl)propanoic acid (585-50-2) → [(R)-1-(7,8-Dihydro-naphthalen-1-yl)-ethyl]-[3-(3-trifluoromethyl-phenyl)-propyl]-amine

Conditions	Yield
Multi-step reaction with 3 steps 1: 85 percent / LAH 2: 65 percent / (COCl)2/DMSO; Et3N View Scheme

Upstream product

• 779-89-5 3-(trifluoromethyl)cinnamic acid 
• 3984-22-3 2-vinyl-1,3-dioxolane 
• 401-78-5 3-bromo-1-trifluoromethylbenzene 
• 294856-02-3 methyl 3-(3-(trifluoromethyl)phenyl)propanoate 
• 95096-06-3 3-(3-(trifluoromethyl)phenyl)propanenitrile 
• 779-89-5 3-(trifluoromethyl)cinnamic acid 
• 705-29-3 3-Trifluoromethylbenzyl chloride 
• 1186194-84-2 dimethyl 2-(3-(trifluoromethyl)benzyl)malonate 
• 402-24-4 3-(trifluoromethyl)styrene 
• 3495-36-1 cesium formate 
• 454-89-7 3-Trifluoromethylbenzaldehyde 

Downstream Products

• 329-02-2 3-[3-(trifluoromethyl)cyclohexyl]propanoic acid 
• 455-03-8 3-(trifluoromethyl)benzenepropanoic acid chloride 
• 78573-45-2 3-[3-(trifluoromethyl)phenyl]propan-1-ol 
• 1005450-55-4 (R)‐N‐(1‐(naphthalen‐1‐yl)ethyl)‐3‐(3‐trifluoromethylphenyl)propanamide 
• 70311-33-0 ethyl 3-(3-trifluoromethylphenyl)-propionate 
• 1076239-83-2 C₁₃H₁₃F₃O₄ 
• 1068558-54-2 (R)-N-(1-(naphthalen-1-yl)-1,2,2,2-d4-ethyl)-3-(3-(trifluoromethyl)phenyl)propanamide hydrochloride 
• 226256-56-0 cinacalcet 
• 21172-43-0 methylsulfonyl-3-(3-trifluoromethylphenyl)propyl ester 
• 1204313-91-6 (R)-tert-butyl (1-(naphthalen-1-yl)ethyl)(3-(3-(trifluoromethyl)phenyl)propyl)carbamate 
• 364782-34-3 cinacalcet hydrochloride 
• 1204313-93-8 (R)-4-nitro-N-(1-naphthalen-1-yl-ethyl)-N-[3-(3-trifluoromethyl-phenyl)-propyl]-benzene sulphonamide 
• 294856-02-3 methyl 3-(3-(trifluoromethyl)phenyl)propanoate 
• 129254-76-8 1-(3-bromopropyl)-3- (trifluoromethyl)benzene 

Relevant academic research and scientific papers

Photoredox Activation of Formate Salts: Hydrocarboxylation of Alkenes via Carboxyl Group Transfer

A photoredox activation mode of formate salts for carboxylation was developed. Using a formate salt as the reductant, carbonyl source, and hydrogen atom transfer reagent, a wide range of alkenes can be converted into acid products via a carboxyl group tra

Hydrogenation reaction method

The invention relates to a hydrogenation reaction method, and belongs to the technical field of organic synthesis. The hydrogenation reaction method provided by the invention comprises the following steps: carrying out a hydrogen transfer reaction on a hydrogen acceptor compound, pinacol borane and a catalyst in a solvent in the presence of proton hydrogen, so that the hydrogen acceptor compound is subjected to a hydrogenation reaction; the catalyst is one or more than two of a palladium catalyst, an iridium catalyst and a rhodium catalyst; the hydrogen acceptor compound comprises one or morethan two functional groups of carbon-carbon double bonds, carbon-carbon triple bonds, carbon-oxygen double bonds, carbon-nitrogen double bonds, nitrogen-nitrogen double bonds, nitryl, carbon-nitrogentriple bonds and epoxy. The method is mild in reaction condition, easy to operate, high in yield, short in reaction time, wide in substrate application range, suitable for carbon-carbon double bonds,carbon-carbon triple bonds, carbon-oxygen double bonds, carbon-nitrogen double bonds, nitrogen-nitrogen double bonds, nitryl, carbon-nitrogen triple bonds and epoxy functional groups, good in selectivity and high in reaction specificity.

Generalized Chemoselective Transfer Hydrogenation/Hydrodeuteration

A generalized, simple and efficient transfer hydrogenation of unsaturated bonds has been developed using HBPin and various proton reagents as hydrogen sources. The substrates, including alkenes, alkynes, aromatic heterocycles, aldehydes, ketones, imines, azo, nitro, epoxy and nitrile compounds, are all applied to this catalytic system. Various groups, which cannot survive under the Pd/C/H2 combination, are tolerated. The activity of the reactants was studied and the trends are as follows: styrene'diphenylmethanimine'benzaldehyde'azobenzene'nitrobenzene'quinoline'acetophenone'benzonitrile. Substrates bearing two or more different unsaturated bonds were also investigated and transfer hydrogenation occurred with excellent chemoselectivity. Nano-palladium catalyst in situ generated from Pd(OAc)2 and HBPin extremely improved the TH efficiency. Furthermore, chemoselective anti-Markovnikov hydrodeuteration of terminal aromatic olefins was achieved using D2O and HBPin via in situ HD generation and discrimination. (Figure presented.).

Preparation method of cinacalcet hydrochloride and intermediate thereof

The invention discloses a preparation method of cinacalcet hydrochloride and an intermediate thereof. The invention provides a preparation method of an intermediate L-cinacalcet tartrate III of cinacalcet hydrochloride. The method comprises the following steps: step (1): in an organic solvent, in the presence of a chiral catalyst and a chiral ligand, an asymmetric hydrogenation reduction reactionis conducted on a cinacalcet intermediate II to obtain cinacalcet IV, wherein the chiral catalyst is bis (1, 5-cyclooctadiene)-rhodium trifluoromethanesulfonate, and the chiral ligand is (S)-3, 3'-bis(2, 4, 6-triisopropylphenyl)-1, 1'-di-2-naphthol cyclic phosphate; and (2) in an organic solvent, a neutralization reaction is conducted between cinacalcet IV and L-tartaric acid to obtain L-cinacalcet tartrate III. The preparation method disclosed by the invention has advantages of short route step, simple and safe operation and high total yield; and the prepared product has high purity, meets the requirements of bulk drugs, is low in production cost and is suitable for industrial production.

Method for synthesizing cinacalcet hydrochloride intermediate in microchannel reactor

The invention provides a method for synthesizing cinacalcet hydrochloride intermediate in a microchannel reactor. The method comprises the steps that 3-(3-trifluoromethylphenyl)-2-acrylic acid and a supported noble metal catalyst are added into an organic solvent A to react with hydrogen to generate 3-(3-trifluoromethylphenyl)propionic acid; after the reaction, filtration is conducted, and a catalyst B and thionyl chloride are added into filtrate to react to generate 3-(3-trifluoromethylphenyl)propionyl chloride, and the two intermediates are all finished in the microchannel reactor. By usingefficient mass transfer and heat transfer of the microchannel reactor, time of hydrogenation is effectively shortened, generation of esterification by-products in the hydrogenation process is prevented, the purity and yield of products are improved, palladium carbon is recovered and applied ,mechanically for many times, cumbersome operation in the kettle reaction process is overcome, and at the same time, materials generated in the reaction can be directly used for the next reaction; and the usage amount of the thionyl chloride in the preparation process of acyl chloride is reduced, waste discharge is reduced, and a green process for synthesizing cinacalcet hydrochloride intermediate is provided.

Preparation method of m-trifluoromethyl phenylpropionic acid

The invention discloses a preparation method of m-trifluoromethyl phenylpropionic acid, which is prepared through catalytic hydrogenation of m-trifluoromethyl cinnamic acid. The catalytic hydrogenation is carried out in the presence of a strong-alkali and weak-acid salt, molar ratio of the strong-alkali and weak-acid salt to the m-trifluoromethyl cinnamic acid being 0.2:1-0.9:1. The strong-alkaliand weak-acid salt preferably is Na2CO3 or K2CO3. In the catalytic hydrogenation of m-trifluoromethyl cinnamic acid, the Na2CO3 or K2CO3 is added according to certain molar ratio, so that generation of benzene ring reduction impurities A, B and C and defluorination impurity D is prevented effectively at the same time, thereby producing the m-trifluoromethyl phenylpropionic acid at high purity, further synthesizing high-purity cinacalcet hydrochloride.

Method for synthesizing calcimimetics hydrochloride intermediates by micro passage reactor

The invention discloses a method for synthesizing calcimimetics hydrochloride intermediates by a micro passage reactor, and belongs to the field of medicine synthesis in organic synthesis. According to the method, p-trifluoromethylcinnamic acid is added into an organic solvent; then, active carbon loaded noble metal catalysts are added; an obtained mixture is used as a first material; the first material is conveyed to a preheating module of the micro passage reactor to be heated; after being preheated, the material enters a reaction module group; hydrogen gas is conveyed to a reaction module group of the micro passage reactor to react with the preheated first material in the step (1) for reaction; reaction liquid flowing out from a temperature lowering module is collected; post treatment is performed to obtain calcimimetics hydrochloride intermediates 3-(3-trifluoromethyl phenyl)propionate. The synthesis method provided by the invention has the advantages that the reaction time can beeffectively shortened; the potential safety hazards of hydrogen leakage combustion blasting is greatly reduced; the method is applicable to the process of synthesizing the calcimimetics hydrochlorideintermediates.

A two-step, one pot preparation of amines via acyl succinimides. Synthesis of the calcimimetic agents cinacalcet, NPS R-467, and NPS R-568

Abstract A method has been developed for the preparation of amines through a process of coupling acyl succinimides derived from commercially available carboxylic acids with amines to afford the corresponding amides. These amides are then reduced in situ with either diisobutylaluminum hydride or lithium aluminum hydride. The reaction tandem of the coupling reaction followed by the reduction affords the amine in fair to good yields after purification by flash chromatography. This one-pot, two reaction tandem process has been successfully applied to the synthesis of the calcimimetic agents cinacalcet, NPS R-467, and NPS R-568.

A novel asymmetric synthesis of cinacalcet hydrochloride

A novel route to asymmetric synthesis of cinacalcet hydrochloride by the application of (R)-tert-butanesulfinamide and regioselective N-alkylation of the naphthyl ethyl sulfinamide intermediate is described.

PROCESS FOR CINACALCET HYDROCHLORIDE

3-[3-(Trifluoromethyl)phenyl]propionaldehyde is a key intermediate for the preparation of cinacalcet hydrochloride. The present invention provides a novel process for the preparation of 3-[3-(trifluoromethyl)phenyl]propionaldehyde. The present invention also provides an improved process for preparation of cinacalcet hydrochloride in high yields. The present invention further provides a process for purification of cinacalcet hydrochloride.