115-46-8

Basic information

• Product Name: alpha,alpha-Diphenyl-4-piperidinomethanol
• Synonyms: TIMTEC-BB SBB003057;4-Piperidinemethanol, alpha,alpha-diphenyl-;alpha,alpha-diphenyl-4-piperidinemethano;Ataractan;Azacyklonol;Calmeran;Diphenyl(4-piperidinyl)methanol;Diphenyl-4-piperidylmethanol
• CAS NO: 115-46-8
• Molecular Formula: C₁₈H₂₁NO
• Molecular Weight: 267.37
• EINECS: 204-092-5
• Product Categories: Pharmaceutical Intermediates;Chemical intermediate for Fexofenadine HCl;INTERMEDIATESOFFEXOFENADINE;(intermediate of fexofenadine hcl);γ-pipradol
• Mol File: 115-46-8.mol
• Article Data: 11

Chemical Properties

• Melting Point: 160-163 °C
• Boiling Point: 410.55°C (rough estimate)
• Flash Point: 142 °C
• Appearance: White to light beige/Solid
• Density: 1.0449 (rough estimate)
• Vapor Pressure: 1.02E-08mmHg at 25°C
• Refractive Index: 1.5100 (estimate)
• Storage Temp.: Store below +30°C.
• Solubility: Chloroform, Methanol (Slightly, Sonicated)
• PKA: 13.32±0.29(Predicted)
• CAS DataBase Reference: alpha,alpha-Diphenyl-4-piperidinomethanol(CAS DataBase Reference)
• NIST Chemistry Reference: alpha,alpha-Diphenyl-4-piperidinomethanol(115-46-8)
• EPA Substance Registry System: alpha,alpha-Diphenyl-4-piperidinomethanol(115-46-8)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 24/25
• WGK Germany: WGK 3 highly water endangering
• RTECS: TN0470000
• Hazardous Substances Data: 115-46-8(Hazardous Substances Data)

Usage

Chemical Properties

white to light beige crystalline powder

Originator

Frenquel,Merrell,US,1955

Uses

Different sources of media describe the Uses of 115-46-8 differently. You can refer to the following data:
1. α-(4-Piperidyl)benzhydrol is a key intermediate in the synthesis of Fexofenadine (F322490). Fexofenadine EP Impurity E.
2. Anxiolytic;H1 antagonist
3. α-(4-Piperidyl)benzhydrol is a key intermediate in the synthesis of Fexofenadine (F322490).

Manufacturing Process

A mixture of 26 g (0.1 mol) of α-(4-pyridyl)-benzhydrol, 1.5 g of platinum oxide, and 250 ml of glacial acetic acid is shaken at 50-60°C under hydrogen at a pressure of 40-50 lb/in2. The hydrogenation is complete in 2 to 3 hours. The solution is filtered and the filtrate evaprated under reduced pressure. The residue is dissolved in a mixture of equal parts of methanol and butanone and 0.1 mol of concentrated hydrochloric acid is added. The mixture is cooled and filtered to give about 30 g of α-(4-piperidyl)benzhydrol hydrochloride, MP 283- 285°C, as a white, crystalline substance. The free base is readily obtained from the hydrochloride salt by treatment with ammonia and when so obtained has a melting point of 160-161°C.

Brand name

Frenquel (Marion Merrell Dow).

Therapeutic Function

Tranquilizer

InChI:InChI=1/C18H21NO/c20-18(15-7-3-1-4-8-15,16-9-5-2-6-10-16)17-11-13-19-14-12-17/h1-10,17,19-20H,11-14H2

Synthetic route

α,α-diphenyl-1-(phenylmethyl)-4-piperidinemethanol (114399-88-1) → C18H21NO (115-46-8)

Conditions	Yield
With hydrogen; palladium on activated charcoal In ethanol at 70℃; under 2585.7 Torr;	99%
palladium In ethanol

N-acetyl-α,α-diphenyl-4-piperidinemethanol (58113-28-3) → C18H21NO (115-46-8)

Conditions	Yield
With hydrogenchloride In ethanol; water at 65 - 97℃; for 12h;	95%

(1-benzyl-1,2,3,6-tetrahydropyridin-4-yl)diphenylmethanol → C18H21NO (115-46-8)

Conditions	Yield
With hydrogen; palladium(II) hydroxide In methanol at 10 - 20℃; under 258.581 Torr; for 5h; Reagent/catalyst; Autoclave;	95%

benzyl 4-(hydroxydiphenylmethyl)-piperidine-1-carboxylate (96067-93-5) → C18H21NO (115-46-8)

Conditions	Yield
With hydrogen; acetic acid; palladium on activated charcoal In ethanol at 25℃; under 3102.89 Torr; for 2.5h; Hydrogenolysis;	88%

ethyl 4-(hydroxydiphenylmethyl)piperidine-1-carboxylate (112818-77-6) → C18H21NO (115-46-8)

Conditions	Yield
With potassium hydroxide In ethanol for 24h; Heating;	75%
In ethanol for 24h; Reflux; Inert atmosphere; Alkaline conditions;	75%

diphenyl(pyridin-4-yl)methanol (1620-30-0) → C18H21NO (115-46-8)

Conditions	Yield
With acetic acid; platinum Hydrogenation;
Multi-step reaction with 5 steps 1: acetone / 20 °C 2: sodium tetrahydroborate / methanol / 4 h / 20 °C 3: cyclohexanol / 2 h / Reflux 4: potassium carbonate / chloroform / 20 °C 5: ethanol / 24 h / Reflux; Inert atmosphere; Alkaline conditions View Scheme
Multi-step reaction with 3 steps 1: acetonitrile / Reflux 2: potassium borohydride / methanol / 3 h / 10 - 20 °C 3: hydrogen; palladium(II) hydroxide / methanol / 5 h / 10 - 20 °C / 258.58 Torr / Autoclave View Scheme
Multi-step reaction with 3 steps 1: acetonitrile / Reflux 2: lithium borohydride / methanol / 3 h / 10 - 20 °C 3: hydrogen; palladium(II) hydroxide / methanol / 5 h / 10 - 20 °C / 258.58 Torr / Autoclave View Scheme

4-carbethoxypiperidine (1126-09-6) → C18H21NO (115-46-8)

Conditions	Yield
Multi-step reaction with 3 steps 1: 99 percent / triethylamine / tetrahydrofuran; H2O / 2 h / 25 °C 2: 73 percent / tetrahydrofuran / 0.83 h / -20 - 20 °C 3: 88 percent / acetic acid; hydrogen / Pd/C / ethanol / 2.5 h / 25 °C / 3102.89 Torr View Scheme

1-benzyl 4-ethyl piperidine-1,4-dicarboxylate (160809-38-1) → C18H21NO (115-46-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: 73 percent / tetrahydrofuran / 0.83 h / -20 - 20 °C 2: 88 percent / acetic acid; hydrogen / Pd/C / ethanol / 2.5 h / 25 °C / 3102.89 Torr View Scheme

VUF 4589 (6071-92-7) → C18H21NO (115-46-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: 70 percent / K2CO3 / CH2Cl2 / Ambient temperature 2: 75 percent / 50percent KOH / ethanol / 24 h / Heating View Scheme
Multi-step reaction with 2 steps 1: potassium carbonate / chloroform / 20 °C 2: ethanol / 24 h / Reflux; Inert atmosphere; Alkaline conditions View Scheme

(1,2,3,6-tetrahydro-1-methylpyridin-4-yl)diphenylmethanol (20735-04-0) → C18H21NO (115-46-8)

Conditions	Yield
Multi-step reaction with 3 steps 1: 85 percent / Ra-Ni / various solvent(s) / 2 h / Heating 2: 70 percent / K2CO3 / CH2Cl2 / Ambient temperature 3: 75 percent / 50percent KOH / ethanol / 24 h / Heating View Scheme
Multi-step reaction with 3 steps 1: cyclohexanol / 2 h / Reflux 2: potassium carbonate / chloroform / 20 °C 3: ethanol / 24 h / Reflux; Inert atmosphere; Alkaline conditions View Scheme

bromobenzene (108-86-1) + radioactive bromine → C18H21NO (115-46-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: 1) Mg / 1) THF, reflux; 2) THF, room temperature, overnight 2: 99 percent / H2 / 5percent Pd/C / ethanol / 70 °C / 2585.7 Torr View Scheme

N-benzyl isonipecotic acid ethyl ester (24228-40-8) → C18H21NO (115-46-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: 1) Mg / 1) THF, reflux; 2) THF, room temperature, overnight 2: 99 percent / H2 / 5percent Pd/C / ethanol / 70 °C / 2585.7 Torr View Scheme

α,α-diphenyl-1-(phenylmethyl)-4-piperidinemethanol (114399-88-1) + di-isopropyl ether (108-20-3) → C18H21NO (115-46-8)

Conditions	Yield
palladium-carbon In ethanol
palladium In ethanol

4-(hydroxy-diphenyl-methyl)-1-methyl-pyridinium iodide (113012-26-3) → C18H21NO (115-46-8)

Conditions	Yield
Multi-step reaction with 4 steps 1: sodium tetrahydroborate / methanol / 4 h / 20 °C 2: cyclohexanol / 2 h / Reflux 3: potassium carbonate / chloroform / 20 °C 4: ethanol / 24 h / Reflux; Inert atmosphere; Alkaline conditions View Scheme

4-Benzoylpyridine (14548-46-0) → C18H21NO (115-46-8)

Conditions	Yield
Multi-step reaction with 6 steps 1: tetrahydrofuran / 20 °C / Inert atmosphere 2: acetone / 20 °C 3: sodium tetrahydroborate / methanol / 4 h / 20 °C 4: cyclohexanol / 2 h / Reflux 5: potassium carbonate / chloroform / 20 °C 6: ethanol / 24 h / Reflux; Inert atmosphere; Alkaline conditions View Scheme

phenylmagnesium bromide (100-58-3) → C18H21NO (115-46-8)

Conditions	Yield
Multi-step reaction with 6 steps 1: tetrahydrofuran / 20 °C / Inert atmosphere 2: acetone / 20 °C 3: sodium tetrahydroborate / methanol / 4 h / 20 °C 4: cyclohexanol / 2 h / Reflux 5: potassium carbonate / chloroform / 20 °C 6: ethanol / 24 h / Reflux; Inert atmosphere; Alkaline conditions View Scheme

isonipecotic acid (498-94-2) → C18H21NO (115-46-8)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: 4 h / Reflux 2.1: thionyl chloride / toluene / 6 h / 40 °C 3.1: aluminum (III) chloride / 10 h / 70 °C 4.1: magnesium; iodine / tetrahydrofuran / Inert atmosphere; Reflux 4.2: 10 - 30 °C / Inert atmosphere 5.1: hydrogenchloride / water; ethanol / 12 h / 65 - 97 °C View Scheme
Multi-step reaction with 5 steps 1.1: 4 h / Reflux 2.1: thionyl chloride / toluene / 6 h / 40 °C 3.1: aluminum (III) chloride / 10 h / 70 °C 4.1: magnesium; iodine / tetrahydrofuran / Inert atmosphere; Reflux 4.2: 10 - 30 °C / Inert atmosphere 5.1: hydrogenchloride / water; ethanol / 12 h / 65 - 97 °C View Scheme
Multi-step reaction with 5 steps 1.1: 6 h / Reflux 2.1: thionyl chloride / toluene / 6 h / 40 °C 3.1: aluminum (III) chloride / 10 h / 70 °C 4.1: magnesium; iodine / tetrahydrofuran / Inert atmosphere; Reflux 4.2: 10 - 30 °C / Inert atmosphere 5.1: hydrogenchloride / water; ethanol / 12 h / 65 - 97 °C View Scheme
Multi-step reaction with 5 steps 1.1: 6 h / Reflux 2.1: thionyl chloride / toluene / 6 h / 40 °C 3.1: aluminum (III) chloride / 10 h / 70 °C 4.1: magnesium; iodine / tetrahydrofuran / Inert atmosphere; Reflux 4.2: 10 - 30 °C / Inert atmosphere 5.1: hydrogenchloride / water; ethanol / 12 h / 65 - 97 °C View Scheme

1-acetyl-piperidine-4-carboxylic acid (25503-90-6) → C18H21NO (115-46-8)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: thionyl chloride / toluene / 6 h / 40 °C 2.1: aluminum (III) chloride / 10 h / 70 °C 3.1: magnesium; iodine / tetrahydrofuran / Inert atmosphere; Reflux 3.2: 10 - 30 °C / Inert atmosphere 4.1: hydrogenchloride / water; ethanol / 12 h / 65 - 97 °C View Scheme
Multi-step reaction with 4 steps 1.1: thionyl chloride / toluene / 6 h / 40 °C 2.1: aluminum (III) chloride / 10 h / 70 °C 3.1: magnesium; iodine / tetrahydrofuran / Inert atmosphere; Reflux 3.2: 10 - 30 °C / Inert atmosphere 4.1: hydrogenchloride / water; ethanol / 12 h / 65 - 97 °C View Scheme

1-(4-benzoylpiperidin-1-yl)ethanone (25519-79-3) → C18H21NO (115-46-8)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: magnesium; iodine / tetrahydrofuran / Inert atmosphere; Reflux 1.2: 10 - 30 °C / Inert atmosphere 2.1: hydrogenchloride / water; ethanol / 12 h / 65 - 97 °C View Scheme

1-acetylpiperidine-4-carbonyl chloride (59084-16-1) → C18H21NO (115-46-8)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: aluminum (III) chloride / 10 h / 70 °C 2.1: magnesium; iodine / tetrahydrofuran / Inert atmosphere; Reflux 2.2: 10 - 30 °C / Inert atmosphere 3.1: hydrogenchloride / water; ethanol / 12 h / 65 - 97 °C View Scheme
Multi-step reaction with 3 steps 1.1: aluminum (III) chloride / 10 h / 70 °C 2.1: magnesium; iodine / tetrahydrofuran / Inert atmosphere; Reflux 2.2: 10 - 30 °C / Inert atmosphere 3.1: hydrogenchloride / water; ethanol / 12 h / 65 - 97 °C View Scheme

isonipecotic acid (498-94-2) + bromobenzene (108-86-1) → C18H21NO (115-46-8)

Conditions	Yield
Stage #1: bromobenzene With magnesium In tetrahydrofuran Reflux; Stage #2: isonipecotic acid In tetrahydrofuran; toluene at 50 - 120℃; under 304.02 - 1140.08 Torr; for 11h; Inert atmosphere;	415 g

pyridine-4-carbonitrile (100-48-1) → C18H21NO (115-46-8)

Conditions	Yield
Multi-step reaction with 4 steps 1: lithium / 5,5-dimethyl-1,3-cyclohexadiene / Inert atmosphere; Reflux 2: acetonitrile / Reflux 3: potassium borohydride / methanol / 3 h / 10 - 20 °C 4: hydrogen; palladium(II) hydroxide / methanol / 5 h / 10 - 20 °C / 258.58 Torr / Autoclave View Scheme
Multi-step reaction with 4 steps 1: lithium / 5,5-dimethyl-1,3-cyclohexadiene / Inert atmosphere; Reflux 2: acetonitrile / Reflux 3: lithium borohydride / methanol / 3 h / 10 - 20 °C 4: hydrogen; palladium(II) hydroxide / methanol / 5 h / 10 - 20 °C / 258.58 Torr / Autoclave View Scheme

benzophenone (119-61-9) → C18H21NO (115-46-8)

Conditions	Yield
Multi-step reaction with 4 steps 1: lithium / 5,5-dimethyl-1,3-cyclohexadiene / Inert atmosphere; Reflux 2: acetonitrile / Reflux 3: potassium borohydride / methanol / 3 h / 10 - 20 °C 4: hydrogen; palladium(II) hydroxide / methanol / 5 h / 10 - 20 °C / 258.58 Torr / Autoclave View Scheme
Multi-step reaction with 4 steps 1: lithium / 5,5-dimethyl-1,3-cyclohexadiene / Inert atmosphere; Reflux 2: acetonitrile / Reflux 3: lithium borohydride / methanol / 3 h / 10 - 20 °C 4: hydrogen; palladium(II) hydroxide / methanol / 5 h / 10 - 20 °C / 258.58 Torr / Autoclave View Scheme

N-benzyl-alpha,alpha-diphenyl-4-pyridinemethanol chloride → C18H21NO (115-46-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: potassium borohydride / methanol / 3 h / 10 - 20 °C 2: hydrogen; palladium(II) hydroxide / methanol / 5 h / 10 - 20 °C / 258.58 Torr / Autoclave View Scheme

C18H21NO (115-46-8) → 4-(diphenylmethylene)piperidine (50706-57-5)

Conditions	Yield
With trifluoroacetic acid In dichloromethane at 20℃;	100%
With trifluoroacetic acid In dichloromethane for 7h; Inert atmosphere;	96%
With trifluoroacetic acid In dichloromethane at 20℃; for 9h;	95%

[4-(4-chloro-1-oxobutyl)phenyl]methyl-propanedioic acid diethyl ester (254453-61-7) + C18H21NO (115-46-8) → [4-[4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]-1-oxobutyl]phenyl]methyl-propanedioic acid diethyl ester

Conditions	Yield
With potassium carbonate In water; toluene for 168h; Heating / reflux;	99%
With potassium carbonate In water; toluene for 168h; Reflux;	99%

C18H21NO (115-46-8) → 4-(hydroxydiphenylmethyl)piperidine-1-sulfamoyl fluoride

Conditions	Yield
With [(4-acetamidophenyl)(fluorosulfonyl)amino]sulfonyl fluoride; 1,8-diazabicyclo[5.4.0]undec-7-ene In tetrahydrofuran at 20℃; for 0.166667h; Reagent/catalyst; Solvent;	98%
With [(4-acetamidophenyl)(fluorosulfonyl)amino]sulfonyl fluoride; 1,8-diazabicyclo[5.4.0]undec-7-ene In tetrahydrofuran at 20℃; for 0.166667h;	96%
With dmap; fluorosulfonyl fluoride; magnesium oxide In dichloromethane; water at 20℃;	94%

4-bromobut-1-yne (38771-21-0) + C18H21NO (115-46-8) → azacyclonol hydrobromide + C22H25NO (476468-82-3)

Conditions	Yield
In tetrahydrofuran at 68℃; for 20h; Heating / reflux;	A n/a B 96.1%

methanesulfonic acid but-3-ynyl ester (72486-09-0) + C18H21NO (115-46-8) → azacyclonol methanesulfonate + C22H25NO (476468-82-3)

Conditions	Yield
In tetrahydrofuran at 68℃; for 20h; Heating / reflux;	A n/a B 95.5%

C18H21NO (115-46-8) + 4-bromobutanenitrile (5332-06-9) → 1-(3-Cyanopropyl)-4-(hydroxydiphenylmethyl)piperidine (118419-86-6)

Conditions	Yield
With potassium carbonate; sodium iodide In butanone for 5h; Heating;	95%

C18H21NO (115-46-8) → 4-(Diphenylmethyl)piperidine (19841-73-7)

Conditions	Yield
With sodium tetrahydroborate; trifluoroacetic acid at 0℃; for 0.75h;	95%
With sodium tetrahydroborate; trifluoroacetic acid In dichloromethane at 0℃; for 0.833333h;	88%
With sodium tetrahydroborate In trifluoroacetic acid
Multi-step reaction with 2 steps 1: trifluoroacetic acid / dichloromethane / 6 h / 20 °C 2: trimethylsilan / dichloromethane / 72 h / 20 °C View Scheme

1-(4-(tert-butyl)phenyl)-3-chloropropan-1-one (28547-33-3) + C18H21NO (115-46-8) → 1-(4-(tert-butyl)phenyl)-3-(4-(hydroxydiphenylmethyl)piperidin-1-yl)propan-1-one

Conditions	Yield
With sodium hydrogencarbonate In water; butanone at 85℃; for 16h;	95%

o-trifluoromethylbenzyl bromide (395-44-8) + C18H21NO (115-46-8) → (1-(2-(trifluoromethyl)benzyl)piperidin-4-yl)diphenylmethanol

Conditions	Yield
With triethylamine In acetonitrile at 70℃; for 4h;	95%

methyl 2-bromomethylbenzoate (2417-73-4) + C18H21NO (115-46-8) → methyl 2-((4-(hydroxydiphenylmethyl)piperidin-1-yl)methyl)benzoate

Conditions	Yield
With triethylamine In acetonitrile at 70℃; for 4h;	95%

formaldehyd (50-00-0) + C18H21NO (115-46-8) → VUF 4589 (6071-92-7)

Conditions	Yield
With sodium tetrahydroborate	94%

2-(3-chloropropyl)-1,3-dioxolane (16686-11-6) + C18H21NO (115-46-8) → {1-[3-(1,3-dioxolan-2-yl)prop-1-yl]piperidin-4-yl}diphenylmethanol (185454-47-1)

Conditions	Yield
With sodium hydrogencarbonate; potassium iodide In N,N-dimethyl-formamide at 50 - 68℃; Alkylation;	94%

C18H21NO (115-46-8) + 4-Nitrophenyl chloroformate (7693-46-1) → 4-nitrophenyl 4-(hydroxydiphenylmethyl)piperidine-1-carboxylate (1209468-67-6)

Conditions	Yield
With triethylamine In dichloromethane at 0℃; for 1h;	94%
With triethylamine In dichloromethane for 2h; Inert atmosphere;	32%

(2-bromoethyl)-4-fluorobenzene (332-42-3) + C18H21NO (115-46-8) → (1-(4-fluorophenethyl)piperidin-4-yl)diphenylmethanol

Conditions	Yield
With triethylamine In acetonitrile at 70℃; for 4h;	94%
With triethylamine In acetonitrile at 85℃; for 19h;	94%

C18H21NO (115-46-8) + 1-bromomethyl-4-iodobenzene (16004-15-2) → (1-(4-iodobenzyl)piperidin-4-yl)diphenylmethanol

Conditions	Yield
With triethylamine In acetonitrile at 70℃; for 4h;	94%

Methyl 4-(bromomethyl)benzoate (2417-72-3) + C18H21NO (115-46-8) → methyl 4-((4-(hydroxydiphenylmethyl)piperidin-1-yl)methyl)benzoate

Conditions	Yield
With triethylamine In acetonitrile at 70℃; for 4h;	92%

C18H21NO (115-46-8) + 2-(6-(tert-butyl)pyridin-3-yl)ethyl 4-methylbenzenesulfonate → (1-(2-(6-(tert-butyl)pyridin-3-yl)ethyl)piperidin-4-yl)diphenylmethanol

Conditions	Yield
With triethylamine In acetonitrile at 70℃; for 4h;	92%
With triethylamine In acetonitrile at 50℃; for 20h;	92%

C18H21NO (115-46-8) + 3-(benzyloxy)-6-bromo-2,4,5-trimethylpyridine (1444336-77-9) → (1-(5-(benzyloxy)-3,4,6-trimethylpyridin-2-yl)piperidin-4-yl)diphenylmethanol

Conditions	Yield
With tris-(dibenzylideneacetone)dipalladium(0); 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; sodium t-butanolate In toluene for 3h; Reflux;	92%

perfluoro-1-butanesulfonyl fluoride (2386-60-9) + C18H21NO (115-46-8) → [1-(butane-1-sulfonyl)piperidin-4-yl]diphenylmethanol (1164112-42-8)

Conditions	Yield
Stage #1: C18H21NO With triethylamine In dichloromethane at 0 - 5℃; for 0.166667h; Stage #2: perfluoro-1-butanesulfonyl fluoride In dichloromethane at 0 - 20℃;	91%

o-fluorobenzyl bromide (446-48-0) + C18H21NO (115-46-8) → (1-(2-fluorobenzyl)piperidin-4-yl)diphenylmethanol

Conditions	Yield
With triethylamine In acetonitrile at 70℃; for 4h;	91%

2-(4-cyclopropanecarbonyl-phenyl)-2-methyl-propionitrile (169280-06-2) + C18H21NO (115-46-8) → 2-(4-(4-(4-(hydroxydiphenylmethyl)piperidin-1-yl)butanoyl)phenyl)-2-methylpropanenitrile (394222-36-7)

Conditions	Yield
With lithium perchlorate In toluene at 150℃; for 4h; Reagent/catalyst; Temperature; Concentration; Solvent;	91%

C18H21NO (115-46-8) + 2-Nitrobenzenesulfonyl chloride (1694-92-4) → [1-(2-nitrobenzenesulfonyl)piperidin-4-yl](diphenyl)methanol (1152785-34-6)

Conditions	Yield
With triethylamine In dichloromethane at 20℃; for 5h;	90%
Stage #1: C18H21NO With triethylamine In dichloromethane at 0 - 5℃; for 0.166667h; Stage #2: 2-Nitrobenzenesulfonyl chloride In dichloromethane at 0 - 20℃;	87%

C18H21NO (115-46-8) + p-toluenesulfonyl chloride (98-59-9) → diphenyl[1-(toluene-4-sulfonyl)piperidin-4-yl]methanol (852860-46-9)

Conditions	Yield
With triethylamine In dichloromethane at 0 - 20℃;	90%
Stage #1: C18H21NO With triethylamine In dichloromethane at 0 - 5℃; for 0.166667h; Stage #2: p-toluenesulfonyl chloride In dichloromethane at 0 - 20℃;	90%

C18H21NO (115-46-8) + benzenesulfonyl chloride (98-09-9) → (1-benzenesulfonylpiperidin-4-yl)diphenylmethanol (950054-08-7)

Conditions	Yield
Stage #1: C18H21NO With triethylamine In dichloromethane at 0 - 5℃; for 0.166667h; Stage #2: benzenesulfonyl chloride In dichloromethane at 0 - 20℃;	90%

2-chloro-3-((4-chlorobenzyl)thio)naphthalene-1,4-dione (1347739-33-6) + C18H21NO (115-46-8) → 2-((4-chlorobenzyl)thio)-3-(4-(hydroxydiphenylmethyl)piperidin-1-yl)naphthalene-1,4-dione (1404074-76-5)

Conditions	Yield
With sodium carbonate In dichloromethane for 4 - 6h;	90%

C18H21NO (115-46-8) + 4-chlorobenzenesulfonyl chloride (98-60-2) → [1-(4-chloro-benzenesulfonyl)-piperidin-4-yl]-diphenylmethanol

Conditions	Yield
Stage #1: C18H21NO With triethylamine In dichloromethane for 0.166667h; Stage #2: 4-chlorobenzenesulfonyl chloride In dichloromethane at 20℃; for 5h; Further stages.;	89%
Stage #1: C18H21NO With triethylamine In dichloromethane at 0 - 5℃; for 0.166667h; Stage #2: 4-chlorobenzenesulfonyl chloride In dichloromethane at 0 - 20℃;	83%

isoxazole-4-sulfonyl chloride (80466-79-1) + C18H21NO (115-46-8) → (1-(3,5-dimethyl-2,3-dihydro-isoxazole-4-sulfonyl)-piperidin-4-yl)-diphenyl-methanol (1164112-38-2)

Conditions	Yield
Stage #1: C18H21NO With triethylamine In dichloromethane at 0 - 5℃; for 0.166667h; Stage #2: isoxazole-4-sulfonyl chloride In dichloromethane at 0 - 20℃;	89%

Upstream product

• 1620-30-0 diphenyl(pyridin-4-yl)methanol 
• 114399-88-1 α,α-diphenyl-1-(phenylmethyl)-4-piperidinemethanol 
• 100-48-1 pyridine-4-carbonitrile 
• 119-61-9 benzophenone 
• 498-94-2 isonipecotic acid 
• 108-86-1 bromobenzene 
• 59084-16-1 1-acetylpiperidine-4-carbonyl chloride 
• 58113-28-3 N-acetyl-α,α-diphenyl-4-piperidinemethanol 
• 25519-79-3 1-(4-benzoylpiperidin-1-yl)ethanone 
• 25503-90-6 1-acetyl-piperidine-4-carboxylic acid 
• 100-58-3 phenylmagnesium bromide 
• 14548-46-0 4-Benzoylpyridine 
• 113012-26-3 4-(hydroxy-diphenyl-methyl)-1-methyl-pyridinium iodide 
• 108-20-3 di-isopropyl ether 

Downstream Products

• 96672-43-4 [1-(Bis-octyloxy-phosphoryl)-[4]piperidyl]-diphenyl-methanol 
• 95228-17-4 (1-diethoxyphosphoryl-[4]piperidyl)-diphenyl-methanol 
• 102476-78-8 3-[4-(α-hydroxy-benzhydryl)-piperidino]-propionic acid methyl ester 
• 99924-97-7 4-(α-hydroxy-benzhydryl)-1,1-dimethyl-piperidinium; iodide 
• 96112-83-3 (1-Dibutoxyphosphoryl-[4]piperidyl)-diphenyl-methanol 
• 1027219-40-4 7-{3-[4-(Hydroxy-diphenyl-methyl)-piperidin-1-yl]-propoxy}-4-oxo-4H-chromene-2-carbonitrile 
• 1027898-47-0 6-{3-[4-(Hydroxy-diphenyl-methyl)-piperidin-1-yl]-propoxy}-4-oxo-4H-chromene-2-carboxylic acid ethyl ester 
• 50706-57-5 4-(diphenylmethylene)piperidine 
• 19841-73-7 4-(Diphenylmethyl)piperidine 
• 154825-96-4 fexofenadine methyl ester 
• 43076-33-1 1-(4-bromophenyl)-4-(4-(hydroxydiphenylmethyl)piperidin-1-yl)butan-1-one 

Relevant articles and documents

Preparation method of alpha, alpha-diphenyl-4-piperidine methanol

The invention discloses a preparation method of alpha, alpha-diphenyl-4-piperidine methanol, which comprises the following steps of by using benzophenone and 4-cyanopyridine as raw materials, carrying out free radical coupling reaction under the action of alkali metal to obtain alpha, alpha-diphenyl-4-piperidine methanol, reacting the obtained alpha, alpha-diphenyl-4-pyridine methanol with a benzylation reagent to generate N-benzyl-alpha, alpha-diphenyl-4-pyridine methanol, carrying out hydroboration reduction on the N-benzyl-alpha, alpha-diphenyl-4-pyridine methanol to obtain (1-benzyl-1, 2, 3, 6-tetrahydropyridine-4-yl)benzhydrol, ane enabling (1-benzyl-1, 2, 3, 6-tetrahydropyridine-4-yl)benzhydrol to be subjected to catalytic hydrogenation and debenzylation protection to obtain alpha, alpha-diphenyl-4-piperidine methanol. The method has the advantages of cheap and accessible raw materials, high reaction yield and high controllability, and is suitable for industrial production requirements.

A α, α-diphenyl-4-piperidine methanol synthesis method

The invention discloses a method for synthesis of alpha,alpha-diphenyl-4-piperidine methanol. The method comprises the steps: taking 4-piperidine formic acid as a raw material, carrying out a reaction with an acetylation reagent to obtain N-acetyl piperidine formic acid; firstly generating N-acetyl piperidine formyl chloride from the obtained N-acetyl piperidine formic acid, and then carrying out a Friedel-Crafts acylation reaction with benzene to generate N-acetyl-4-benzoyl piperidine; carrying out a Grignard reaction of the obtained N-acetyl-4-benzoyl piperidine with phenyl magnesium halide to obtain N-acetyl-alpha,alpha-diphenyl-4-piperidine methanol; and deacetylating the N-acetyl-alpha,alpha-diphenyl-4-piperidine methanol to obtain the alpha,alpha-diphenyl-4-piperidine methanol. The synthesis method has the characteristics of cheap and easily obtained raw materials, simple process steps, high reaction yield and low costs of raw materials, and is suitable for industrialized production.

Synthesis of terfenadine carboxylate

A synthesis of terfenadine carboxylate, 1, a metabolite of terfenadine 2, is described. In the key step, the sodium salt of 2-(4-bromo-phenyl)-2-methylpropionic acid, 7, was lithiated via a metal-halogen exchange using t-BuLi and subsequently condensed with 4-[4-(hydroxydiphenylmethylpiperidin-1-yl]butyraldehyde, 5, to afford terfenadine carboxylate, 1.