78573-45-2

Basic information

• Product Name: 3-(3'-TRIFLUOROMETHYL PHENYL) PROPANOL
• Synonyms: 3-(3'-TRIFLUOROMETHYL PHENYL) PROPANOL;3-(3-TRIFLUOROMETHYL-PHENYL)-PROPAN-1-OL;3-(Trifluoromethyl)benzenepropanol;Cinacalcet Intermediate 1;Cinacalcet I;Cinacalcet InterMediates;3-(3-(trifluoroMrthyl)pheny1)propan-1-ol;3-(3-Hydroxyprop-1-yl)benzotrifluoride, 3-(3-Hydroxyprop-1-yl)-alpha,alpha,alpha-trifluorotoluene
• CAS NO: 78573-45-2
• Molecular Formula: C₁₀H₁₁F₃O
• Molecular Weight: 204.1889496
• EINECS: 1592732-453-0
• Product Categories: Aromatics Compounds;Aromatics;Intermediates;Cinacalcet Intermediate
• Mol File: 78573-45-2.mol
• Article Data: 30

Chemical Properties

• Boiling Point: 68-71℃/0.4mm
• Flash Point: 104.666 °C
• Appearance: Colorless/Liquid
• Density: 1.10
• Refractive Index: 1.4620 to 1.4660
• Storage Temp.: Sealed in dry,Room Temperature
• Solubility: DMSO (Slightly), Methanol (Slightly)
• PKA: 15.04±0.10(Predicted)
• CAS DataBase Reference: 3-(3'-TRIFLUOROMETHYL PHENYL) PROPANOL(CAS DataBase Reference)
• NIST Chemistry Reference: 3-(3'-TRIFLUOROMETHYL PHENYL) PROPANOL(78573-45-2)
• EPA Substance Registry System: 3-(3'-TRIFLUOROMETHYL PHENYL) PROPANOL(78573-45-2)

Safety Data

• Hazardous Substances Data: 78573-45-2(Hazardous Substances Data)

Usage

Chemical Properties

Brown Oil

Uses

3-(Trifluoromethyl)benzenepropanol-d4 is an intermediate in the synthesis of Cinacalcet-d4 Hydrochloride (C441803), a labeled analogue of Cinacalcet Hydrochloride (C441800), the (R) enantiomer of Cinacalcet which is used in clinical trial in secondary hyperparathyroidism.

Synthetic route

3-<3-(trifluoromethyl)phenyl>prop-2-en-1-ol (64189-17-9) → 3-[3-(trifluoromethyl)phenyl]propan-1-ol (78573-45-2)

Conditions	Yield
With hydrogen In ethanol at 60℃; under 15001.5 Torr; for 6h; Pressure; Temperature; Solvent; Autoclave;	99.4%
With hydrogen; palladium on activated charcoal In ethanol at 20℃; under 750.06 Torr; for 26h;	57%
With 5%-palladium/activated carbon In 2-methyltetrahydrofuran at 30 - 40℃; under 1500.15 - 2250.23 Torr; Temperature;

methyl 3-(3-(trifluoromethyl)phenyl)propanoate (294856-02-3) → 3-[3-(trifluoromethyl)phenyl]propan-1-ol (78573-45-2)

Conditions	Yield
With hydrogen In methanol at 160℃; under 150015 Torr; Product distribution / selectivity;	98%
With lithium aluminium tetrahydride In diethyl ether at 0℃;	97%
With dimethylsulfide borane complex In 2-methyltetrahydrofuran at 90℃; under 7500.75 Torr; for 0.333333h; Inert atmosphere; Flow reactor;	97%
Stage #1: methyl 3-(3-(trifluoromethyl)phenyl)propanoate With sodium tetrahydroborate In tetrahydrofuran Inert atmosphere; Reflux; Stage #2: With methanol In tetrahydrofuran at 60 - 65℃; for 9h; Inert atmosphere;	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-(trifluoromethyl)phenyl)prop-2-yn-1-ol (65126-85-4) → 3-[3-(trifluoromethyl)phenyl]propan-1-ol (78573-45-2)

Conditions	Yield
With palladium 10% on activated carbon; hydrogen In ethanol at 20℃; for 6h;	82%
With hydrogen; palladium 10% on activated carbon In isopropyl alcohol at 42 - 45℃; under 3750.38 Torr; for 5h;	72.1%
With hydrogen; 5% Pd(II)/C(eggshell) In methanol at 20℃; under 760.051 Torr; for 72h;
With hydrogen; 5% Pd(II)/C(eggshell) In methanol; water at 20℃; under 760.051 Torr; for 72h;

(R)-1-(meta-trifluoromethylphenyl) 3-tosyloxy 2-propanol (154775-01-6) → meta-trifluoromethylphenyl-propane (41320-75-6) + 3-[3-(trifluoromethyl)phenyl]propan-1-ol (78573-45-2) + (S)-1-[(3′-trifluoromethyl)phenyl]-2-propanol (135561-75-0)

Conditions	Yield
With lithium aluminium tetrahydride In diethyl ether at 21℃; for 3h;	A 3% B 8% C 69%

2-[2-(3-Trifluoromethyl-phenyl)-ethyl]-oxirane → 3-[3-(trifluoromethyl)phenyl]propan-1-ol (78573-45-2)

Conditions	Yield
Multi-step reaction with 3 steps 1: aq. HClO4 / tetrahydrofuran 2: Pb(OAc)4 / CH2Cl2 3: LiAlH4 / diethyl ether View Scheme

ethyl 3-(3-trifluoromethylphenyl)-propionate (70311-33-0) + 3-[3-(trifluoromethyl)phenyl]propanal (21172-41-8) → 3-[3-(trifluoromethyl)phenyl]propan-1-ol (78573-45-2)

Conditions	Yield
Stage #1: ethyl 3-(3-trifluoromethylphenyl)-propionate; 3-[3-(trifluoromethyl)phenyl]propanal With sodium tetrahydroborate In ethanol at 20℃; for 24h; Stage #2: With ethanol; water In ethyl acetate Product distribution / selectivity;

ethyl 3-(3-trifluoromethylphenyl)-propionate (70311-33-0) → 3-[3-(trifluoromethyl)phenyl]propan-1-ol (78573-45-2)

Conditions	Yield
Stage #1: ethyl 3-(3-trifluoromethylphenyl)-propionate With sodium tetrahydroborate In ethanol at 20℃; for 24h; Stage #2: With ethanol; water In ethyl acetate Product distribution / selectivity;

ethyl 3-(3-trifluoromethylphenyl)-propionate (70311-33-0) + (E)-3-(3-(trifluoromethyl)phenyl)acrylaldehyde (262268-58-6) → 3-[3-(trifluoromethyl)phenyl]propan-1-ol (78573-45-2) + (E)-3-(3-trifluoromethylphenyl)prop-2-en-1-ol (113048-69-4)

Conditions	Yield
Stage #1: ethyl 3-(3-trifluoromethylphenyl)-propionate; (E)-3-(3-(trifluoromethyl)phenyl)acrylaldehyde With sodium tetrahydroborate In ethanol at 20℃; for 24h; Stage #2: With ethanol; water In ethyl acetate Product distribution / selectivity;
Stage #1: ethyl 3-(3-trifluoromethylphenyl)-propionate; (E)-3-(3-(trifluoromethyl)phenyl)acrylaldehyde With lithium aluminium tetrahydride In tetrahydrofuran at -5℃; for 0.666667h; Stage #2: With sodium hydroxide; water In tetrahydrofuran; acetone Product distribution / selectivity;
Stage #1: ethyl 3-(3-trifluoromethylphenyl)-propionate; (E)-3-(3-(trifluoromethyl)phenyl)acrylaldehyde With lithium aluminium tetrahydride In tetrahydrofuran at -5℃; for 0.666667h; Stage #2: With sulfuric acid; water In tetrahydrofuran; acetone Product distribution / selectivity;

3-Trifluoromethylbenzaldehyde (454-89-7) → 3-[3-(trifluoromethyl)phenyl]propan-1-ol (78573-45-2)

Conditions	Yield
Multi-step reaction with 3 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 3.1: borane / tetrahydrofuran / 25 h / 0 - 20 °C / Inert atmosphere View Scheme
Multi-step reaction with 4 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 3.1: thionyl chloride / 4 h / Inert atmosphere; Reflux 4.1: sodium tetrahydroborate / tetrahydrofuran / Inert atmosphere; Reflux 4.2: 9 h / 60 - 65 °C / Inert atmosphere View Scheme

3-(trifluoromethyl)cinnamic acid (779-89-5) → 3-[3-(trifluoromethyl)phenyl]propan-1-ol (78573-45-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: hydrogen / palladium 10% on activated carbon / methanol / 2.5 h / 750.08 Torr 2: borane / tetrahydrofuran / 25 h / 0 - 20 °C / Inert atmosphere View Scheme
Multi-step reaction with 2 steps 1: palladium 10% on activated carbon; hydrogen / ethanol / 16 h / 20 °C / 760.05 Torr 2: lithium aluminium tetrahydride / tetrahydrofuran / 2 h / 20 °C View Scheme
Multi-step reaction with 3 steps 1.1: sodium hydroxide / water / 20 °C 1.2: 7 h / 25 - 30 °C / 750.08 Torr 1.3: pH 2 2.1: thionyl chloride / 4 h / Inert atmosphere; Reflux 3.1: sodium tetrahydroborate / tetrahydrofuran / Inert atmosphere; Reflux 3.2: 9 h / 60 - 65 °C / Inert atmosphere View Scheme

3-trifluoromethylbenzoic acid methyl ester (2557-13-3) → 3-[3-(trifluoromethyl)phenyl]propan-1-ol (78573-45-2)

Conditions	Yield
Multi-step reaction with 3 steps 1: potassium methanolate / iso-xylene / 12 h / 80 °C / 760.05 Torr / Industry scale 2: hydrogen / 5% Pd(II)/C(eggshell) / methanol / 48 h / 60 °C / 7500.75 Torr / Autoclave 3: hydrogen / / methanol / 160 °C / 150015 Torr View Scheme

3-bromo-1-trifluoromethylbenzene (401-78-5) → 3-[3-(trifluoromethyl)phenyl]propan-1-ol (78573-45-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: triethylamine / triphenylphosphine; copper(l) iodide; palladium dichloride / N,N-dimethyl acetamide / 50 - 70 °C / Inert atmosphere 2: hydrogen / 5% Pd(II)/C(eggshell) / methanol / 72 h / 20 °C / 760.05 Torr View Scheme
Multi-step reaction with 2 steps 1: triethylamine / triphenylphosphine; copper(l) iodide; palladium dichloride / ISOPROPYLAMIDE / 17 h / 50 - 70 °C 2: hydrogen / 5% Pd(II)/C(eggshell) / water; methanol / 72 h / 20 °C / 760.05 Torr View Scheme
Multi-step reaction with 2 steps 1: copper(l) iodide; 1,8-diazabicyclo[5.4.0]undec-7-ene; tetrakis(triphenylphosphine) palladium(0) / tetrahydrofuran / 22 h / 0 - 55 °C / Inert atmosphere; Sealed tube 2: palladium 10% on activated carbon; hydrogen / ethanol / 6 h / 20 °C View Scheme

3-[3-(trifluoromethyl)phenyl]propan-1-ol (78573-45-2) + methanesulfonyl chloride (124-63-0) → methylsulfonyl-3-(3-trifluoromethylphenyl)propyl ester (21172-43-0)

Conditions	Yield
With triethylamine In dichloromethane at 20℃;	100%
With triethylamine In dichloromethane at -5℃; for 1.5h; Temperature;	97.9%
With triethylamine In toluene at 20 - 25℃; for 2h;	93%

3-[3-(trifluoromethyl)phenyl]propan-1-ol (78573-45-2) → 3-[3-(trifluoromethyl)phenyl]propanal (21172-41-8)

Conditions	Yield
Stage #1: 3-[3-(trifluoromethyl)phenyl]propan-1-ol With phosphorus pentoxide; dimethyl sulfoxide In dichloromethane at 20℃; Swern Oxidation; Cooling with ice; Stage #2: With triethylamine In dichloromethane at 20℃; Cooling with ice;	100%
Stage #1: 3-[3-(trifluoromethyl)phenyl]propan-1-ol With phosphorus pentoxide; dimethyl sulfoxide In dichloromethane for 0.5h; Cooling; Stage #2: With triethylamine In dichloromethane for 1h; Cooling;	100%
With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; trichloroisocyanuric acid at 0 - 20℃; for 0.5h;	100%

3-[3-(trifluoromethyl)phenyl]propan-1-ol (78573-45-2) + p-toluenesulfonyl chloride (98-59-9) → 3-(3-trifluoromethylphenyl)propyl 4-methylphenylsulfonate

Conditions	Yield
With triethylamine In dichloromethane at 20℃; Autoclave; Large scale;	100%
With pyridine In chloroform
With triethylamine; dmap In dichloromethane at -5 - 10℃; Product distribution / selectivity;
With triethylamine; dmap In dichloromethane at 25 - 40℃; for 15h; Product distribution / selectivity;

3-[3-(trifluoromethyl)phenyl]propan-1-ol (78573-45-2) + (R)-(+)-1-(1-naphthyl)ethyl o-nitrobenzenesulfonamide → ((1R)-1-(1-naphthyl)ethyl) N-(3-(3-(trifluoromethyl)phenyl)propyl)-o-nitrobenzenesulfonamide

Conditions	Yield
With triphenylphosphine; diethylazodicarboxylate In toluene at 50℃; for 1h;	100%

(R)-1-(1-Naphthyl)ethylamine (3886-70-2) + 3-[3-(trifluoromethyl)phenyl]propan-1-ol (78573-45-2) → cinacalcet (226256-56-0)

Conditions	Yield
With bis[dichloro(pentamethylcyclopentadienyl)iridium(III)]; D-sorbitol; choline chloride at 60℃; for 12h;	98%
Stage #1: 3-[3-(trifluoromethyl)phenyl]propan-1-ol With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; [bis(acetoxy)iodo]benzene In dichloromethane at 20℃; for 2h; Stage #2: (R)-1-(1-Naphthyl)ethylamine With sodium tris(acetoxy)borohydride In dichloromethane optical yield given as %ee;	84%
With bis[dichloro(pentamethylcyclopentadienyl)iridium(III)]; sodium hydrogencarbonate In toluene at 110℃; for 17h; Inert atmosphere; Sealed tube;	75%
With C19H22MnN3O3P(1+); potassium hydride In 1,2-dimethoxyethane at 100℃; for 48h; Glovebox; Sealed tube; Inert atmosphere;	50%

3-[3-(trifluoromethyl)phenyl]propan-1-ol (78573-45-2) → 1-(3-bromopropyl)-3- (trifluoromethyl)benzene (129254-76-8)

Conditions	Yield
With sulfuric acid; hydrogen bromide; tetra(n-butyl)ammonium hydrogensulfate In water at 82℃; for 25h; Temperature; Concentration; Reagent/catalyst;	90.97%
With hydrogen bromide In water at 85 - 90℃; for 15h;	82%
With 1H-imidazole; bromine; triphenylphosphine In dichloromethane at 0 - 25℃;	81%

3-[3-(trifluoromethyl)phenyl]propan-1-ol (78573-45-2) → 1-(3-iodopropyl)-3-(trifluoromethyl)benzene (566938-58-7)

Conditions	Yield
With 1H-imidazole; iodine; triphenylphosphine In dichloromethane at 20 - 35℃; for 2h;	85%
With trimethylsilyl iodide In dichloromethane at 20℃;

(R)-1-(1-Naphthyl)ethylamine (3886-70-2) + 3-[3-(trifluoromethyl)phenyl]propan-1-ol (78573-45-2) → cinacalcet hydrochloride (364782-34-3)

Conditions	Yield
Stage #1: (R)-1-(1-Naphthyl)ethylamine; 3-[3-(trifluoromethyl)phenyl]propan-1-ol With bis[dichloro(pentamethylcyclopentadienyl)iridium(III)] In toluene at 110℃; for 6h; Inert atmosphere; Stage #2: With hydrogenchloride In diethyl ether; hexane; ethyl acetate; toluene Reagent/catalyst; Time;	83%

3-[3-(trifluoromethyl)phenyl]propan-1-ol (78573-45-2) → 1-[(1E)-3-bromopropyl-1-en-1-yl]-3-(trifluoromethyl)benzene + 1-(3-bromopropyl)-3- (trifluoromethyl)benzene (129254-76-8)

Conditions	Yield
With sulfuric acid; hydrogen bromide In water at 25 - 55℃;	A n/a B 76.45%

3-[3-(trifluoromethyl)phenyl]propan-1-ol (78573-45-2) + 2-(pyrimidin-5-yl)phenol → 5-(2-(3-(3-(trifluoromethyl)phenyl)propoxy)phenyl)pyrimidine

Conditions	Yield
With di-isopropyl azodicarboxylate; triphenylphosphine In toluene at 20℃; for 12h; Sealed tube;	67%

3-[3-(trifluoromethyl)phenyl]propan-1-ol (78573-45-2) + C13H12ClNO → (R)-(1-naphthalen-1-ylethyl)carbamic acid 3-(3-trifluoromethylphenyl)propyl ester (915979-44-1)

Conditions	Yield
With pyridine In dichloromethane at -2 - 22℃; for 16.5h; Temperature; Inert atmosphere;	48.17%

3-[3-(trifluoromethyl)phenyl]propan-1-ol (78573-45-2) + methyl (S)-2-tert-butoxycarbonyl-7-hydroxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylate (262616-16-0) → methyl (S)-2-tert-butoxycarbonyl-7-[3-(3-trifluoromethylphenyl)propoxy]-1,2,3,4-tetrahydroisoquinoline-3-carboxylate

Conditions	Yield
With triphenylphosphine; diethylazodicarboxylate In tetrahydrofuran; toluene at 20℃; for 2h; Mitsunobu Displacement;	40%

3-[3-(trifluoromethyl)phenyl]propan-1-ol (78573-45-2) → [(S)-1-(7,8-Dihydro-naphthalen-1-yl)-ethyl]-[3-(3-trifluoromethyl-phenyl)-propyl]-amine

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

3-[3-(trifluoromethyl)phenyl]propan-1-ol (78573-45-2) → [(R)-1-(7,8-Dihydro-naphthalen-1-yl)-ethyl]-[3-(3-trifluoromethyl-phenyl)-propyl]-amine

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

3-[3-(trifluoromethyl)phenyl]propan-1-ol (78573-45-2) → Acetylamino-<3-(m-trifluormethyl-phenyl)-propyl-(1)>-malonsaeure-diaethylester

Conditions	Yield
Multi-step reaction with 2 steps 1: Py 2: (i) Na, KI, EtOH, (ii) /BRN= 2987616/ View Scheme

3-[3-(trifluoromethyl)phenyl]propan-1-ol (78573-45-2) → 2-Amino-5-(3-trifluoromethyl-phenyl)-pentanoic acid

Conditions	Yield
Multi-step reaction with 3 steps 1: Py 2: (i) Na, KI, EtOH, (ii) /BRN= 2987616/ 3: aq. HCl View Scheme

Upstream product

• 21172-41-8 3-[3-(trifluoromethyl)phenyl]propanal 
• 64189-17-9 3-<3-(trifluoromethyl)phenyl>prop-2-en-1-ol 
• 713-71-3 2-<3-(trifluoromethyl)benzyl>oxirane 
• 154775-01-6 (R)-1-(meta-trifluoromethylphenyl) 3-tosyloxy 2-propanol 
• 585-50-2 3-(3-trifluoromethylphenyl)propanoic acid 
• 779-89-5 3-(trifluoromethyl)cinnamic acid 
• 113048-69-4 (E)-3-(3-trifluoromethylphenyl)prop-2-en-1-ol 
• 154309-48-5 1-<3-(trifluoromethyl)phenyl>prop-2-en-1-ol 
• 154902-50-8 (R)-1-(meta-trifluoromethylphenyl) 2,3-propanediol 
• 113048-70-7 (1S,2S)-1-(meta-trifluoromethylphenyl) 1,2-epoxy-3-propanol 
• 70311-33-0 ethyl 3-(3-trifluoromethylphenyl)-propionate 
• 262268-58-6 (E)-3-(3-(trifluoromethyl)phenyl)acrylaldehyde 
• 65126-85-4 3-(3-(trifluoromethyl)phenyl)prop-2-yn-1-ol 
• 454-89-7 3-Trifluoromethylbenzaldehyde 

Downstream Products

• 21172-43-0 methylsulfonyl-3-(3-trifluoromethylphenyl)propyl ester 
• 21172-41-8 3-[3-(trifluoromethyl)phenyl]propanal 
• 82258-76-2 1-(3-chloropropyl)-3-(trifluoromethyl)benzene 
• 129254-76-8 1-(3-bromopropyl)-3- (trifluoromethyl)benzene 
• 226256-56-0 cinacalcet 
• 364782-34-3 cinacalcet hydrochloride 
• 1204313-91-6 (R)-tert-butyl (1-(naphthalen-1-yl)ethyl)(3-(3-(trifluoromethyl)phenyl)propyl)carbamate 
• 1204313-93-8 (R)-4-nitro-N-(1-naphthalen-1-yl-ethyl)-N-[3-(3-trifluoromethyl-phenyl)-propyl]-benzene sulphonamide 
• 566938-58-7 1-(3-iodopropyl)-3-(trifluoromethyl)benzene 

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