[ CAS No. 124937-73-1 ] {[proInfo.proName]}

Name: 124937-73-1|3-(2-Methoxy-5-methylphenyl)-3-phenylpropan-1-ol|98%
Brand: Ambeed
SKU: A221498
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Quality Control of [ 124937-73-1 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 124937-73-1 ]

SDS Specification

Alternatived Products of [ 124937-73-1 ]

Product Details of [ 124937-73-1 ]

CAS No. :	124937-73-1	MDL No. :	MFCD08063882
Formula :	C₁₇H₂₀O₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	OCGTUTJXBDQGKL-UHFFFAOYSA-N
M.W :	256.34	Pubchem ID :	11161175
Synonyms :

Calculated chemistry of [ 124937-73-1 ]

Physicochemical Properties

Num. heavy atoms :	19
Num. arom. heavy atoms :	12
Fraction Csp3 :	0.29
Num. rotatable bonds :	5
Num. H-bond acceptors :	2.0
Num. H-bond donors :	1.0
Molar Refractivity :	78.13
TPSA :	29.46 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	Yes
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-5.28 cm/s

Lipophilicity

Log Po/w (iLOGP) :	2.95
Log Po/w (XLOGP3) :	3.64
Log Po/w (WLOGP) :	3.52
Log Po/w (MLOGP) :	3.43
Log Po/w (SILICOS-IT) :	4.34
Consensus Log Po/w :	3.57

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	0.0
Bioavailability Score :	0.55

Water Solubility

Log S (ESOL) :	-3.86
Solubility :	0.0354 mg/ml ; 0.000138 mol/l
Class :	Soluble
Log S (Ali) :	-3.95
Solubility :	0.029 mg/ml ; 0.000113 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-5.72
Solubility :	0.000493 mg/ml ; 0.00000192 mol/l
Class :	Moderately soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	2.61

Safety of [ 124937-73-1 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P280-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302-H315-H319-H332-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 124937-73-1 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

Upstream synthesis route of [ 124937-73-1 ]
Downstream synthetic route of [ 124937-73-1 ]

[ 124937-73-1 ] Synthesis Path-Upstream 1~5

1
[ 75-21-8 ]
[ 124937-73-1 ]

Yield	Reaction Conditions	Operation in experiment
100%	Stage #1: With n-butyllithium In tetrahydrofuran at -78 - 20℃; for 4 h; Stage #2: With water; ammonium chloride In tetrahydrofuran	BuLi (54.4 ml, 0.147 mol) was added to a solution of (2-methoxy-5-methylphenyl)phenylmethane (24 g, 0.113 mol), in 120 ml of THF at -78°C. Once the addition was complete, it was heated to room temperature and maintained at said temperature for about 2 hours. The temperature was again reduced to -78°C and ethylene oxide (4.98 g, 0.113 mol) was added such that the temperature did not exceed - 50°C. The reaction was allowed to take place, being complete after 2 hours. Then the mixture was hydrolyzed with 60 ml of NH₄Cl, extracted with 30 ml of ethyl acetate, the organic phase was washed with 2x25 ml of NH₄Cl, dried and evaporated, giving 30 g (100percent) of a viscous yellow liquid containing the title compound.

Reference： [1] Patent: EP1698615, 2006, A1, . Location in patent: Page/Page column 9

2
[ 109089-77-2 ]
[ 124937-73-1 ]

Yield	Reaction Conditions	Operation in experiment
97%	Stage #1: With sodium tetrahydroborate In tetrahydrofuran at 20℃; Stage #2: With methanesulfonic acid In tetrahydrofuran at 20 - 70℃;	A solution of 0.5 kg 3-(2-methoxy-5-methylphenyl) -3-phenyl propionic acid in 2.0 L tetrahydrofuran was added drop wise in the suspension of 0.105 kg sodium borohydride in 0.5 L tetrahydrofuran within 2 hrs. After completion of addition, reaction mixture was stirred at RT for 2 hrs. 0.177 kg methanesulfonic acid was added drop wise within 1 hrs. After completion of addition, reaction mixture was stirred at RT for 1 hr. The reaction mixture was stirred at 65-7O0C for 8-10 hrs. After completion of reaction, reaction mixture was cooled at 0-50C. The reaction mixture was acidified with 0.25 L IM aq. HCl up to pH 2-3, and then reaction mixture was extracted with ethyl acetate (1 L x 2). The organic layers were washed with 2.0 L water 2.0 L brine. The solvent was distilled out to dryness at reduced pressure (30-40 mm Hg) to obtain 3-(2-methoxy-5-methylphenyl)-3-phenyl propanol (Yield: 0.462 kg, 97percent)[167] HPLC Purity > 95percent.
85%	Stage #1: With sodium tetrahydroborate In tetrahydrofuran at 20℃; Stage #2: With sulfuric acid In tetrahydrofuran at 20 - 70℃;	Example 2 [158] Preparation of 3-(2-methoxy-5-methylphenyl)-3-phenyl propanol; [159](III) (IV) [161] [162] A solution of 0.5 kg of 3-(2-methoxy-5-methylphenyl)-3-phenyl propionic acid in 1.5 L tetrahydrofuran was added drop wise in the suspension of 0.105 Kg of sodium borohydride in 1 L ml tetrahydrofuran under stirring within 2-4 hrs. After completion of addition, reaction mixture was stirred at RT for 2 hrs. 0.181 Kg of Cone. Sulfuric acid was added drop wise within 2-3 hrs. After completion of addition, reaction mixture was stirred at RT for 1-2 hr. The reaction mixture was stirred at 65-7O0C for 6-10 hrs. After completion of reaction, reaction mixture was cooled to 25-3O0C. Saturated brine solution was added to reaction mass and the solution was stirred for 15 min. The organic layer was separated out and distilled it completely. The reaction mass was mixed with aqueous layer and then extracted with dichloromethane (IL x 2). The organic layers were combined and washed with 1 L water ; 1 L brine. The solvent was distilled out to dryness at reduced pressure (30-40 mm Hg) to obtain 3 - (2-methoxy- 5 -methylphenyl) -3 -phenyl propanol.[163] (Yield 0402 Kg, 85percent) [164] HPLC Purity >; 96percent

Reference： [1] Patent: WO2010/46801, 2010, A2, . Location in patent: Page/Page column 16
[2] Patent: WO2010/92500, 2010, A2, . Location in patent: Paragraph 157-164

3
[ 50-00-0 ]
[ 389068-20-6 ]
[ 124937-73-1 ]

Reference： [1] Angewandte Chemie - International Edition, 2016, vol. 55, # 21, p. 6315 - 6318[2] Angew. Chem., 2016, vol. 128, p. 6423 - 6426,4

4
[ 7083-19-4 ]
[ 124937-73-1 ]

Reference： [1] Organic Letters, 2016, vol. 18, # 2, p. 252 - 255

5
[ 40546-94-9 ]
[ 124937-73-1 ]

Reference： [1] Patent: US2012/41235, 2012, A1,

[ 124937-73-1 ] Synthesis Path-Downstream 1~18

1
[ 124937-73-1 ]
[ 98-59-9 ]
[ 124937-85-5 ]

Yield	Reaction Conditions	Operation in experiment
85%	With triethylamine; In dichloromethane; at 0 - 20℃;	Example 3 [167] Preparation of 3-(2-methoxy-5-methylphenyl)-3-phenyl propyl-p-toluene sulphonate(IV); (V)[169] [170] 0.45 kg <strong>[124937-73-1]3-(2-methoxy-5-methylphenyl)-3-phenyl propanol</strong> in 2.25 L dichloromethane was stirred and cooled at O0C under stirring.0.27 kg triethylamine was added drop wise to the reaction mixture.0.388 kg p-toluene sulfonylchloride was added to the reaction mixture. The reaction mixture was stirred at 0-50C for 1 hr and then at RT for 5-8 hrs. After the completion of reaction, the reaction mixture was acidified with 0.25 L IM aq.HCl up to pH 2-3.Then reaction mixture was extracted with dichloromethane (0.5L x 2).The combined organic layers was washed with 1.0 L DM water, 1.0 L brine &; dried over 0.25 kg sodium sulfate. The solvent was completely distilled out at reduced pressure (30-40 mm Hg). Crude 0.78 kg3-(2-methoxy-5-methylphenyl)-3-phenyl propyl-p-toluene sulphonate was dissolved in isopropyl alcohol (1.56 L) and heat it up to 800C for 2-3 hrs and then cool it at RT. The solid was filtered &; washed with isopropyl alcohol (0.450 L). The solid was dried at50-550C to obtain pure 3-(2-methoxy-5-methylphenyl)-3-phenyl propyl-p-toluene sulphonate.[171] Dry wt= 0.616 Kg [172] Yield=85% [173] Purity by HPLC= >;98% [174]
77%	With triethylamine; In dichloromethane; at 0 - 20℃;	0.45 kg 3-(2-methoxy-5- methylphenyl) -3-phenyl propanol in 2.25 L dichloromethane was stirred and cooled at 00C under stirring. 0.27 kg triethyl amine was added drop wise to the reaction mixture. 0.388 kg p-toluene sulfonylchloride was added to the reaction mixture. The reaction mixture was stirred at 00C for 1 hrs, then at RT for 4-5 hrs. After the completion of reaction, the reaction mixture was acidified with 0.25 L IM aq. HCl up to pH 2-3. Then reaction mixture was extracted with dichloromethane (0.5 L x 2). The combined organic layers was washed with 1.0 L DM water, 1.0 lit brine & dried over 0.25 kg sodium sulfate. The solvent was completely distilled out at reduced pressure (30-40 mm Hg). Crude 3-(2-methoxy- 5-methylphenyl) -3-phenyl propyl-p-toluene sulphonate was triturated with 1.5 lit di- isopropylether at 00C for 4-5 hrs to obtain a solid. The solid was filtered & washed with chilled 0.3 L diisopropyl ether. The solid was dried at 50-550C to obtain 3-(2-methoxy-5-methylphenyl)-3-phenyl propyl-p-toluene sulphonate (Yield: 0.553 kg, 77%).[183] HPLC Purity > 95 %.
	With triethylamine; In MDC; at -5 - 0℃; for 5h;	Intermediate 4; Synthesis of Toluene-4-sulfonic acid-3-(2-methoxy-5-methel-phenel .-3-phenyl propyl ester; MDC (200 ml) and Intermediate 3 (100 gms) were charged in a clean dry flask under nitrogen and stirred. 175 ml TEA was added and the reaction mixture cooled to about-5C. A solution of 190 gms p-toluene sulfonyl chloride in 500 ml MDC was charged slowly over 2 hours at-5C to 0C. The reaction mixture was stirred for 3 hours. After completion of reaction, 250 ml of water was charged below 10C. The organic layer was separated and washed with 2 x 150 ml of 2N HC1 and finally with 3 x 200 ml of water. The organic layer was dried and concentrated under vacuum below 45C to obtain an oil. The oil was dissolved in a mixture of 100 ml acetone and 600 ml n-hexane and slowly cooled to 5C and stirred for 2 hours. The solids were filtered and dried at 50C under vacuum for 4 hours to obtain the title compound (135-138 gms).

	With pyridine; In chloroform; at -10 - 0℃;	EXAMPLE 8 Preparation of tolterodine from 3-(2-hydroxy-5-methyl-phenyl)-3-phenylpropionic acid methyl ester (V) The compound 3-(2-hydroxy-5-methyl-phenyl)-3-phenylpropionic acid methyl ester (44 g 0.163 mol) is refluxed for 24 hours in a mixture consisting of 75 ml of methanol, 75 ml of acetone containing methyl iodide (25 g, 0.175 mol) and potassium carbonate (13.75 g, 0.1 mol). Afterwards, the solid is filtered off and the solvent is evaporated off. The residue is dissolved in ether and washed with water. The solvent is evaporated off to obtain 40 g of an oil which is redissolved in ether (75 ml) and slowly dropped in a solution of lithium aluminium hydride (5.6 g, 0.147 g) in 150 ml of anhydrous ether. The mixture is left under stirring overnight. Afterwards the lithium aluminium hydride excess is destroyed with water and 15% sodium hydroxide. The precipitate is filtered off and solvent is evaporated off to obtain 35 g of an oil corresponding to the propanol derivative. The resulting oil is dissolved in 50 ml of chloroform containing 15 ml of pyridine and the mixture is cooled to -10 C. p-Toluenesulfonyl chloride (14 g, 0.07 mols) is dropped therein and the mixture is reacted at -5/0 C. overnight, then poured in ice/water. The organic phase is separated, washed with diluted hydrochloric acid and distilled under vacuum at a temperature below 50 C. The resulting low-melting solid, that is the tosyl-derivative, is placed in autoclave together with 50 ml of acetonitrile and 50 g of diisopropylamine. After heating the mixture at 80 C. for a week, volatile solvents are evaporated off. The residue is treated with 2N sodium hydroxide and extracted with ether. The product is extracted from the ether phase with a 2N HCl solution. After further washings with ether, the acidic phase is adjusted to basic pH with sodium hydroxide and the product is re-extracted with ether. The organic solution is then evaporated to give an oil (20 g) corresponding to tolterodine phenol-protected as the methyl ether. Said oil is finally dissolved in dichloromethane (75 ml), cooled to 0 C. and treated with a IN solution of boron tribromide in dichloromethane (32 ml 0.032 mols). The mixture is kept one week under stirring in thermocryostat at temperatures ranging from 0 to 5 C. Afterwards, the solvent is evaporated off and the residue is partitioned in a basic water/ether mixture. The organic solvent is evaporated off to obtain an oil which is purified by flash chromatography (eluent hexane-ethyl acetate 7:3) and is tolterodine free base.
	With pyridine; In chloroform; at -5 - 0℃;	Example 8: Preparation of tolterodine from 3-(2-hydroxy-5-methylphenyl)-3-phenylpropionic acid methyl ester (V) The compound 3-(2-hydroxy-5-methyl-phenyl)-3-phenylpropionic acid methyl ester (44 g 0.163 mol) is refluxed for 24 hours in a mixture consisting of 75 ml of methanol, 75 ml of acetone containing methyl iodide (25 g, 0.175 mol) and potassium carbonate (13.75 g, 0.1 mol). Afterwards, the solid is filtered off and the solvent is evaporated off. The residue is dissolved in ether and washed with water. The solvent is evaporated off to obtain 40 g of an oil which is redissolved in ether (75 ml) and slowly dropped in a solution of lithium aluminium hydride (5.6 g, 0.147 g) in 150 ml of anhydrous ether. The mixture is left under stirring overnight. Afterwards the lithium aluminium hydride excess is destroyed with water and 15% sodium hydroxide. The precipitate is filtered off and solvent is evaporated off to obtain 35 g of an oil corresponding to the propanol derivative. The resulting oil is dissolved in 50 ml of chloroform containing 15 ml of pyridine and the mixture is cooled to -10C. p-Toluenesulfonyl chloride (14 g, 0.07 mols) is dropped therein and the mixture is reacted at -5/0C overnight, then poured in ice/water. The organic phase is separated, washed with diluted hydrochloric acid and distilled under vacuum at a temperature below 50C. The resulting low-melting solid, that is the tosyl-derivative, is placed in autoclave together with 50 ml of acetonitrile and 50 g of diisopropylamine. After heating the mixture at 80C for a week, volatile solvents are evaporated off. The residue is treated with 2N sodium hydroxide and extracted with ether. The product is extracted from the ether phase with a 2N HCl solution. After further washings with ether, the acidic phase is adjusted to basic pH with sodium hydroxide and the product is re-extracted with ether. The organic solution is then evaporated to give an oil (20 g) corresponding to tolterodine phenol-protected as the methyl ether. Said oil is finally dissolved in dichloromethane (75 ml), cooled to 0C and treated with a 1N solution of boron tribromide in dichloromethane (32 ml 0.032 mols). The mixture is kept one week under stirring in thermocryostat at temperatures ranging from 0 to 5C. Afterwards, the solvent is evaporated off and the residue is partitioned in a basic water/ether mixture. The organic solvent is evaporated off to obtain an oil which is purified by flash chromatography (eluent hexane - ethyl acetate 7:3) and is tolterodine free base.

Reference： [1]Patent: WO2010/92500,2010,A2 .Location in patent: Paragraph 166-173
[2]Angewandte Chemie - International Edition,2016,vol. 55,p. 6315 - 6318
Angew. Chem.,2016,vol. 128,p. 6423 - 6426,4
[3]Patent: WO2010/46801,2010,A2 .Location in patent: Page/Page column 17-18; 10
[4]Patent: WO2005/61432,2005,A1 .Location in patent: Page/Page column 13
[5]Patent: US2006/189827,2006,A1 .Location in patent: Page/Page column 5-6
[6]Patent: EP1693361,2006,A1 .Location in patent: Page/Page column 8-9

2
2-(3-hydroxy-5-methyl-phenyl)-propionic acid methyl ester [ No CAS ]
[ 124937-73-1 ]

Yield	Reaction Conditions	Operation in experiment
		Intermediate 3; Synthesis of 3- (2-methox5-methyl-phenvl)-3-phenyl-propan-1-ol; THF (200 ml) and 16 gms of sodium borohydride were charged to a clean dry flask under nitrogen. The mixture was cooled to about-10C and 100 gms of Intermediate 2 dissolved in 250 ml tetrahydrofuran was added slowly at a temperature in the range of 0C to-10C over 2-3 hours. 72 ml of boron trifluoride etherate was charged slowly over 3 hours maintaining the temperature between 0C to 5C. After completion of addition, the temperature was slowly raised to between 25C to 30 C and the reaction mass stirred for 2 hours. After completion of reaction, the reaction mixture was cooled to about 5C and 3 M hydrochloric acid solution was added slowly to adjust the pH to between 1-3. The reaction mixture was filtered. The clear filtrate was concentrated under vacuum to give the title compound as an oil (95 gms).

Reference： [1]Patent: WO2005/61432,2005,A1 .Location in patent: Page/Page column 12-13

3
[ 124937-73-1 ]
[ 124-63-0 ]
[ 882878-66-2 ]

Yield	Reaction Conditions	Operation in experiment
90%		EXAMPLE 6 Preparation of 3-(2-methoxy-5-methylphenyl)-3-phenylpropyl-methanesulfonate (V, R=CH3) The propanol of the formula (IV) (R=Me) (20 g, 0.083 moles) was dissolved in methylene chloride (300 ml). The solution was cooled to 0 C. and triethylamine (12.5 g, 0.124 moles) and methanesulfonyl chloride (10.3 g, 0.091 moles) were added in quick succession. The reaction mixture was left to stand at ambient temperature for 20 h, then cooled to 0 C. and water (200 ml) and dilute HCl (2N) (100 ml) were added. The organic phase was separated and washed with water (2*100 ml). The solvent was removed under reduced pressure and the crude product crystallized from MTBE (150 ml) to yield 23.9 g of 3-(2-methoxy-5-methylphenyl)-3-phenylpropyl-methanesulfonate (V) as a white solid (yield 90%).
		Example 1: Preparation of 3-(2-methoxy-5-methylphenyl)-3-phenylpropyl methane sulfonate (Vb)This intermediate is of significant importance for use in the preparation of Tolterodine or salts thereof, or its derivatives according to the present invention.In a 3-necked round bottom flask, 6-methyl-4-phenyl-3,4-dihydro coumarin (II, 10Og, 0.420 mol) is charged into methanol (500 ml) at about 250C with stirring. To the resulting suspension, potassium carbonate (K2CO3, 87 g, 0.63 mol) and methyl iodide (MeI, 78 ml, 1.25 mol) are added and the mass is stirred at from about 550C to about 6O0C for 4 h. The reaction mass is cooled to from about 400C to about 450C and MeI (27 ml, 0.43 mol) and K2CO3 (29 g, 0.21 mol) are added. Re-heat the mass to 55~ 6O0C and stir for additional 6 h until the reaction completes. Then solvent is removed by distillation under vacuum. The residue is dissolved in 350 ml of toluene. This organic phase is washed once with 750 ml of DM water and twice with 450 ml of DM water.The organic layer thus obtained is charged into a 3-necked round bottom flask under N2 atmosphere and cooled at temperature from about -50C to about 5C. Toluene solution of sodium bis(2-methoxyethoxy) aluminum hydride (Red-Al, 200 ml, 70% w/v, 0.706 mol) is slowly added through a dropping funnel over a period of 120 min, maintaining the solution temperature within -5 ~ 50C. The mixture is stirred for an additional 1 h at this temperature until the reaction completes. Then aqueous solution of NaOH (80 ml, 10%) is added through a dropping funnel over a period of 45 min, maintaining the temperature at 0 ~ 100C, and continue stirring for an additional 45 min at the same temperature. Add 750 ml of DM water and stir for 30 min at 250C. The biphasic reaction mass is filtered through a celite bed (10 g). The organic layer is collected and dried over 20 g of anhydrous sodium sulfate (Na2SO4). The solids are filtered and washed with 50 ml of toluene. The toluene is distilled off completely and compound IV is obtained as slightly yellow thick oil.The thick oil is dissolved in 300 ml of dichloromethane (DCM) under N2 atmosphere. Triethylamine (Et3N, 90 ml, 0.647 mol) is added and the mass is cooled to 0 ~ 5C. Mesyl chloride (MsCl, 36 ml, 0.465 mol) is added slowly through a dropping funnel over a period of 120 min, keeping the solution temperature below 1O0C. Continue stirring the mixture for an additional 1 h at 0~5C until the reaction completes. 1 L of cold DM water (0~5C) was added and the mass is stirred for 30 ~ 60 min at this temperature. Cone. HCl (25 ml) is added and the mass is stirred until it reaches 25C. The organic layer is collected and washed with 200 ml of DM water. About 180 ~ 220 ml of DCM is distilled off from the organic layer under atmosphere pressure at 38 ~ 43C. 400 ml of cyclohexane is added to the residue and the mass is heated to reflux till a clear solution is obtained (70 ~ 800C). This solution is cooled slowly and compound Vb crystallized. The solid is filtered in Buchner funnel and spray washed with 100 ml of cold cyclohexane. The mass is dried under vacuum at 600C to give 90 ~ 110 g of title compound.
	With triethylamine; In dichloromethane; at 0 - 10℃; for 3h;Inert atmosphere;	Example 1; Preparation of 3-(2-methoxy-5-methylphenyl)-3-phenylpropyl methane sulfonate (Vb); This intermediate is of significant importance for use in the preparation of Tolterodine or salts thereof, or its derivatives according to the present invention.In a 3-necked round bottom flask, 6-methyl-4-phenyl-3,4-dihydro coumarin (II, 100 g, 0.420 mol) is charged into methanol (500 ml) at about 25 C. with stirring. To the resulting suspension, potassium carbonate (K2CO3, 87 g, 0.63 mol) and methyl iodide (MeI, 78 ml, 1.25 mol) are added and the mass is stirred at from about 55 C. to about 60 C. for 4 h. The reaction mass is cooled to from about 40 C. to about 45 C. and MeI (27 ml, 0.43 mol) and K2CO3 (29 g, 0.21 mol) are added. Re-heat the mass to 5560 C. and stir for additional 6 h until the reaction completes. Then solvent is removed by distillation under vacuum. The residue is dissolved in 350 ml of toluene. This organic phase is washed once with 750 ml of DM water and twice with 450 ml of DM water.The organic layer thus obtained is charged into a 3-necked round bottom flask under N2 atmosphere and cooled at temperature from about -5 C. to about 5 C. Toluene solution of sodium bis(2-methoxyethoxy) aluminum hydride (Red-Al, 200 ml, 70% w/v, 0.706 mol) is slowly added through a dropping funnel over a period of 120 min, maintaining the solution temperature within -55 C. The mixture is stirred for an additional 1 h at this temperature until the reaction completes. Then aqueous solution of NaOH (80 ml, 10%) is added through a dropping funnel over a period of 45 min, maintaining the temperature at 010 C., and continue stirring for an additional 45 min at the same temperature. Add 750 ml of DM water and stir for 30 min at 25 C. The biphasic reaction mass is filtered through a celite bed (10 g). The organic layer is collected and dried over 20 g of anhydrous sodium sulfate (Na2SO4). The solids are filtered and washed with 50 ml of toluene. The toluene is distilled off completely and compound IV is obtained as slightly yellow thick oil.The thick oil is dissolved in 300 ml of dichloromethane (DCM) under N2 atmosphere. Triethylamine (Et3N, 90 ml, 0.647 mol) is added and the mass is cooled to 05 C. Mesyl chloride (MsCl, 36 ml, 0.465 mol) is added slowly through a dropping funnel over a period of 120 min, keeping the solution temperature below 10 C. Continue stirring the mixture for an additional 1 h at 05 C. until the reaction completes. 1 L of cold DM water (05 C.) was added and the mass is stirred for 3060 min at this temperature. Conc. HCl (25 ml) is added and the mass is stirred until it reaches 25 C. The organic layer is collected and washed with 200 ml of DM water. About 180220 ml of DCM is distilled off from the organic layer under atmosphere pressure at 3843 C. 400 ml of cyclohexane is added to the residue and the mass is heated to reflux till a clear solution is obtained (7080 C.). This solution is cooled slowly and compound Vb crystallized. The solid is filtered in Buchner funnel and spray washed with 100 ml of cold cyclohexane. The mass is dried under vacuum at 60 C. to give 90110 g of title compound.

Reference： [1]Patent: US2006/79716,2006,A1 .Location in patent: Page/Page column 7-8
[2]Patent: WO2010/94292,2010,A1 .Location in patent: Page/Page column 6
[3]Patent: US2012/41235,2012,A1 .Location in patent: Page/Page column 4

4
methyl 3-(2-methoxy-5-methylphenyl)-3-phenylpropionate [ No CAS ]
[ 124937-73-1 ]

Yield	Reaction Conditions	Operation in experiment
		EXAMPLE 8 Preparation of tolterodine from 3-(2-hydroxy-5-methyl-phenyl)-3-phenylpropionic acid methyl ester (V) The compound 3-(2-hydroxy-5-methyl-phenyl)-3-phenylpropionic acid methyl ester (44 g 0.163 mol) is refluxed for 24 hours in a mixture consisting of 75 ml of methanol, 75 ml of acetone containing methyl iodide (25 g, 0.175 mol) and potassium carbonate (13.75 g, 0.1 mol). Afterwards, the solid is filtered off and the solvent is evaporated off. The residue is dissolved in ether and washed with water. The solvent is evaporated off to obtain 40 g of an oil which is redissolved in ether (75 ml) and slowly dropped in a solution of lithium aluminium hydride (5.6 g, 0.147 g) in 150 ml of anhydrous ether. The mixture is left under stirring overnight. Afterwards the lithium aluminium hydride excess is destroyed with water and 15% sodium hydroxide. The precipitate is filtered off and solvent is evaporated off to obtain 35 g of an oil corresponding to the propanol derivative. The resulting oil is dissolved in 50 ml of chloroform containing 15 ml of pyridine and the mixture is cooled to -10 C. p-Toluenesulfonyl chloride (14 g, 0.07 mols) is dropped therein and the mixture is reacted at -5/0 C. overnight, then poured in ice/water. The organic phase is separated, washed with diluted hydrochloric acid and distilled under vacuum at a temperature below 50 C. The resulting low-melting solid, that is the tosyl-derivative, is placed in autoclave together with 50 ml of acetonitrile and 50 g of diisopropylamine. After heating the mixture at 80 C. for a week, volatile solvents are evaporated off. The residue is treated with 2N sodium hydroxide and extracted with ether. The product is extracted from the ether phase with a 2N HCl solution. After further washings with ether, the acidic phase is adjusted to basic pH with sodium hydroxide and the product is re-extracted with ether. The organic solution is then evaporated to give an oil (20 g) corresponding to tolterodine phenol-protected as the methyl ether. Said oil is finally dissolved in dichloromethane (75 ml), cooled to 0 C. and treated with a IN solution of boron tribromide in dichloromethane (32 ml 0.032 mols). The mixture is kept one week under stirring in thermocryostat at temperatures ranging from 0 to 5 C. Afterwards, the solvent is evaporated off and the residue is partitioned in a basic water/ether mixture. The organic solvent is evaporated off to obtain an oil which is purified by flash chromatography (eluent hexane-ethyl acetate 7:3) and is tolterodine free base.
		Example 1: Preparation of 3-(2-methoxy-5-methylphenyl)-3-phenylpropyl methane sulfonate (Vb)This intermediate is of significant importance for use in the preparation of Tolterodine or salts thereof, or its derivatives according to the present invention.In a 3-necked round bottom flask, 6-methyl-4-phenyl-3,4-dihydro coumarin (II, 10Og, 0.420 mol) is charged into methanol (500 ml) at about 250C with stirring. To the resulting suspension, potassium carbonate (K2CO3, 87 g, 0.63 mol) and methyl iodide (MeI, 78 ml, 1.25 mol) are added and the mass is stirred at from about 550C to about 6O0C for 4 h. The reaction mass is cooled to from about 400C to about 450C and MeI (27 ml, 0.43 mol) and K2CO3 (29 g, 0.21 mol) are added. Re-heat the mass to 55~ 6O0C and stir for additional 6 h until the reaction completes. Then solvent is removed by distillation under vacuum. The residue is dissolved in 350 ml of toluene. This organic phase is washed once with 750 ml of DM water and twice with 450 ml of DM water.The organic layer thus obtained is charged into a 3-necked round bottom flask under N2 atmosphere and cooled at temperature from about -50C to about 5C. Toluene solution of sodium bis(2-methoxyethoxy) aluminum hydride (Red-Al, 200 ml, 70% w/v, 0.706 mol) is slowly added through a dropping funnel over a period of 120 min, maintaining the solution temperature within -5 ~ 50C. The mixture is stirred for an additional 1 h at this temperature until the reaction completes. Then aqueous solution of NaOH (80 ml, 10%) is added through a dropping funnel over a period of 45 min, maintaining the temperature at 0 ~ 100C, and continue stirring for an additional 45 min at the same temperature. Add 750 ml of DM water and stir for 30 min at 250C. The biphasic reaction mass is filtered through a celite bed (10 g). The organic layer is collected and dried over 20 g of anhydrous sodium sulfate (Na2SO4). The solids are filtered and washed with 50 ml of toluene. The toluene is distilled off completely and compound IV is obtained as slightly yellow thick oil.The thick oil is dissolved in 300 ml of dichloromethane (DCM) under N2 atmosphere. Triethylamine (Et3N, 90 ml, 0.647 mol) is added and the mass is cooled to 0 ~ 5C. Mesyl chloride (MsCl, 36 ml, 0.465 mol) is added slowly through a dropping funnel over a period of 120 min, keeping the solution temperature below 1O0C. Continue stirring the mixture for an additional 1 h at 0~5C until the reaction completes. 1 L of cold DM water (0~5C) was added and the mass is stirred for 30 ~ 60 min at this temperature. Cone. HCl (25 ml) is added and the mass is stirred until it reaches 25C. The organic layer is collected and washed with 200 ml of DM water. About 180 ~ 220 ml of DCM is distilled off from the organic layer under atmosphere pressure at 38 ~ 43C. 400 ml of cyclohexane is added to the residue and the mass is heated to reflux till a clear solution is obtained (70 ~ 800C). This solution is cooled slowly and compound Vb crystallized. The solid is filtered in Buchner funnel and spray washed with 100 ml of cold cyclohexane. The mass is dried under vacuum at 600C to give 90 ~ 110 g of title compound.
	With lithium aluminium tetrahydride; In diethyl ether;	Example 8: Preparation of tolterodine from 3-(2-hydroxy-5-methylphenyl)-3-phenylpropionic acid methyl ester (V) The compound 3-(2-hydroxy-5-methyl-phenyl)-3-phenylpropionic acid methyl ester (44 g 0.163 mol) is refluxed for 24 hours in a mixture consisting of 75 ml of methanol, 75 ml of acetone containing methyl iodide (25 g, 0.175 mol) and potassium carbonate (13.75 g, 0.1 mol). Afterwards, the solid is filtered off and the solvent is evaporated off. The residue is dissolved in ether and washed with water. The solvent is evaporated off to obtain 40 g of an oil which is redissolved in ether (75 ml) and slowly dropped in a solution of lithium aluminium hydride (5.6 g, 0.147 g) in 150 ml of anhydrous ether. The mixture is left under stirring overnight. Afterwards the lithium aluminium hydride excess is destroyed with water and 15% sodium hydroxide. The precipitate is filtered off and solvent is evaporated off to obtain 35 g of an oil corresponding to the propanol derivative. The resulting oil is dissolved in 50 ml of chloroform containing 15 ml of pyridine and the mixture is cooled to -10C. p-Toluenesulfonyl chloride (14 g, 0.07 mols) is dropped therein and the mixture is reacted at -5/0C overnight, then poured in ice/water. The organic phase is separated, washed with diluted hydrochloric acid and distilled under vacuum at a temperature below 50C. The resulting low-melting solid, that is the tosyl-derivative, is placed in autoclave together with 50 ml of acetonitrile and 50 g of diisopropylamine. After heating the mixture at 80C for a week, volatile solvents are evaporated off. The residue is treated with 2N sodium hydroxide and extracted with ether. The product is extracted from the ether phase with a 2N HCl solution. After further washings with ether, the acidic phase is adjusted to basic pH with sodium hydroxide and the product is re-extracted with ether. The organic solution is then evaporated to give an oil (20 g) corresponding to tolterodine phenol-protected as the methyl ether. Said oil is finally dissolved in dichloromethane (75 ml), cooled to 0C and treated with a 1N solution of boron tribromide in dichloromethane (32 ml 0.032 mols). The mixture is kept one week under stirring in thermocryostat at temperatures ranging from 0 to 5C. Afterwards, the solvent is evaporated off and the residue is partitioned in a basic water/ether mixture. The organic solvent is evaporated off to obtain an oil which is purified by flash chromatography (eluent hexane - ethyl acetate 7:3) and is tolterodine free base.

With sodium bis(2-methoxyethoxy)aluminium dihydride; In toluene; at -5 - 5℃; for 3h;Inert atmosphere;

Example 1; Preparation of 3-(2-methoxy-5-methylphenyl)-3-phenylpropyl methane sulfonate (Vb); This intermediate is of significant importance for use in the preparation of Tolterodine or salts thereof, or its derivatives according to the present invention.In a 3-necked round bottom flask, 6-methyl-4-phenyl-3,4-dihydro coumarin (II, 100 g, 0.420 mol) is charged into methanol (500 ml) at about 25 C. with stirring. To the resulting suspension, potassium carbonate (K2CO3, 87 g, 0.63 mol) and methyl iodide (MeI, 78 ml, 1.25 mol) are added and the mass is stirred at from about 55 C. to about 60 C. for 4 h. The reaction mass is cooled to from about 40 C. to about 45 C. and MeI (27 ml, 0.43 mol) and K2CO3 (29 g, 0.21 mol) are added. Re-heat the mass to 5560 C. and stir for additional 6 h until the reaction completes. Then solvent is removed by distillation under vacuum. The residue is dissolved in 350 ml of toluene. This organic phase is washed once with 750 ml of DM water and twice with 450 ml of DM water.The organic layer thus obtained is charged into a 3-necked round bottom flask under N2 atmosphere and cooled at temperature from about -5 C. to about 5 C. Toluene solution of sodium bis(2-methoxyethoxy) aluminum hydride (Red-Al, 200 ml, 70% w/v, 0.706 mol) is slowly added through a dropping funnel over a period of 120 min, maintaining the solution temperature within -55 C. The mixture is stirred for an additional 1 h at this temperature until the reaction completes. Then aqueous solution of NaOH (80 ml, 10%) is added through a dropping funnel over a period of 45 min, maintaining the temperature at 010 C., and continue stirring for an additional 45 min at the same temperature. Add 750 ml of DM water and stir for 30 min at 25 C. The biphasic reaction mass is filtered through a celite bed (10 g). The organic layer is collected and dried over 20 g of anhydrous sodium sulfate (Na2SO4). The solids are filtered and washed with 50 ml of toluene. The toluene is distilled off completely and compound IV is obtained as slightly yellow thick oil.The thick oil is dissolved in 300 ml of dichloromethane (DCM) under N2 atmosphere. Triethylamine (Et3N, 90 ml, 0.647 mol) is added and the mass is cooled to 05 C. Mesyl chloride (MsCl, 36 ml, 0.465 mol) is added slowly through a dropping funnel over a period of 120 min, keeping the solution temperature below 10 C. Continue stirring the mixture for an additional 1 h at 05 C. until the reaction completes. 1 L of cold DM water (05 C.) was added and the mass is stirred for 3060 min at this temperature. Conc. HCl (25 ml) is added and the mass is stirred until it reaches 25 C. The organic layer is collected and washed with 200 ml of DM water. About 180220 ml of DCM is distilled off from the organic layer under atmosphere pressure at 3843 C. 400 ml of cyclohexane is added to the residue and the mass is heated to reflux till a clear solution is obtained (7080 C.). This solution is cooled slowly and compound Vb crystallized. The solid is filtered in Buchner funnel and spray washed with 100 ml of cold cyclohexane. The mass is dried under vacuum at 60 C. to give 90110 g of title compound.

Reference： [1]Patent: US2006/189827,2006,A1 .Location in patent: Page/Page column 5-6
[2]Patent: WO2010/94292,2010,A1 .Location in patent: Page/Page column 6
[3]Patent: EP1693361,2006,A1 .Location in patent: Page/Page column 8-9
[4]Patent: US2012/41235,2012,A1 .Location in patent: Page/Page column 4

5
[ 124937-73-1 ]
3-(2-methoxy-5-methylphenyl)-3-phenylpropanal [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
94%		Dimethylsulfoxide (DMSO) (6.72 ml, 94.6 mmol) in 20 ml of Cl2CH2 was added to a mixture of oxalyl chloride (4.06 ml, 47.3 mmol) in 100 ml of Cl2CH2 and cooled at -78C, always maintaining the reaction temperature under -60C. It was allowed to take place at said temperature for 15 minutes and then a mixture of <strong>[124937-73-1]3-(2-methoxy-5-methylphenyl)-3-phenylpropanol</strong> (9.33g, 36.4 mmol) in 40ml of Cl2CH2 was added. The reaction mixture was maintained for about 45 minutes and triethylamine (25.72 ml, 0.18 mol) was added. The crude reaction product was maintained reacting for about 1 hour and hydrolyzed with 100 ml of NaHCO3 (7%). The extraction was carried out with 100 ml of ethyl acetate. The organic phase was washed with 2x25ml of HCl (5%), dried and evaporated, giving 8.67g (94%) of a viscous orangish liquid containing the title compound.
	With pyridine-SO3 complex; triethylamine; In dichloromethane; dimethyl sulfoxide; at 0℃;Product distribution / selectivity;	SO3·Py (1.56 g, 9.75 mmol) was slowly added to a mixture at 0C consisting of <strong>[124937-73-1]3-(2-methoxy-5-methylphenyl)-3-phenylpropanol</strong> (0.5 g, 1.95 mmol), 6.5 ml of Cl2CH2, 0.54 ml of DMSO and triethylamine (2.7 ml, 19.5 mmol). Once the reaction concluded, it was washed with a NH4Cl saturated solution (2x25 ml). The resulting organic phase was dried and the solvent was evaporated, giving 0.45 g of a black viscous liquid containing the title compound.
	With magnesium sulfate; pyridinium chlorochromate; In dichloromethane; for 3h;Product distribution / selectivity;	<strong>[124937-73-1]3-(2-methoxy-5-methylphenyl)-3-phenylpropanol</strong> (0.5 g, 1.95 mmol) dissolved in 1 ml of Cl2CH2 was added to a suspension of PCC (0.63 g, 2.93 mmol) and 0.5 g of MgSO4 in 4 ml of Cl2CH2. The reaction was completed after 3 hours. Then it was filtered with celite and the filtrate was extracted with 2x25 ml of HCl (5%). The resulting organic phase was dried and the solvent was evaporated, giving 2.21 g of a dark viscous liquid containing the title compound.

With sodium hypochlorite; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; 3-chloro-benzenecarboperoxoic acid; In dichloromethane; water; at -10 - 0℃; for 1h;pH 9.5;Product distribution / selectivity;

Metachloroperbenzoic acid (0.04 g, 0.213 mmol) was added to a mixture consisting of 2.5 ml of Cl2CH2 and 2,2,6,6-tetramethyl-piperidine (TMPP) N-oxide (3 mg, 0.022 mmol) at -10C, and subsequently <strong>[124937-73-1]3-(2-methoxy-5-methylphenyl)-3-phenylpropanol</strong> (0.5 g, 1.95 mmol) dissolved in 2.5 ml of Cl2CH2 was added dropwise, maintaining the temperature at -10C. Then the temperature was increased to 0C and a 10% NaOCl solution (1.3 ml, 2.13 mmol) at pH 9.5 was added dropwise, maintaining the reaction for 1 hour. Once this time elapsed, the reaction mixture was treated with water and Cl2CH2, giving 0.4 g of an impure, dense yellow liquid containing the compound of the title.

Reference： [1]Patent: EP1698615,2006,A1 .Location in patent: Page/Page column 9
[2]Patent: EP1698615,2006,A1 .Location in patent: Page/Page column 9
[3]Patent: EP1698615,2006,A1 .Location in patent: Page/Page column 9
[4]Patent: EP1698615,2006,A1 .Location in patent: Page/Page column 9

6
[ 75-21-8 ]
(2-methoxy-5-methylphenyl)phenylmethane [ No CAS ]
[ 124937-73-1 ]

Yield	Reaction Conditions	Operation in experiment
100%		BuLi (54.4 ml, 0.147 mol) was added to a solution of (2-methoxy-5-methylphenyl)phenylmethane (24 g, 0.113 mol), in 120 ml of THF at -78C. Once the addition was complete, it was heated to room temperature and maintained at said temperature for about 2 hours. The temperature was again reduced to -78C and ethylene oxide (4.98 g, 0.113 mol) was added such that the temperature did not exceed - 50C. The reaction was allowed to take place, being complete after 2 hours. Then the mixture was hydrolyzed with 60 ml of NH4Cl, extracted with 30 ml of ethyl acetate, the organic phase was washed with 2x25 ml of NH4Cl, dried and evaporated, giving 30 g (100%) of a viscous yellow liquid containing the title compound.

Reference： [1]Patent: EP1698615,2006,A1 .Location in patent: Page/Page column 9

Yield	Reaction Conditions	Operation in experiment
		e) 3-(2-Methoxy-5-methylphenyl)-3-phenylpropanol (XX) was obtained in a similar way as an oil in quantitative yield from the ester (X) of Example 2e). NMR: delta 6.8-7.4 (m 7H), 4.7 (t 1H), 3.8 (s 3H), 3.7 (m 2H), 2.3 (s 3H), 2.0-2.3 (m 2H).
		e) 3-(2-Methoxy-5-methylphenyl)-3-phenylpropanol (XX) was obtained in a similar way as an oil in quantitative yield from the ester (X) of Example 2e). NMR: delta 6.8-7.4 (m 7H), 4.7 (t 1H), 3.8 (s 3H), 3.7 (m 2H), 2.3 (s 3H), 2.0-2.3 (m 2H).

8
[ 109089-77-2 ]
[ 124937-73-1 ]

Yield	Reaction Conditions	Operation in experiment
97%		A solution of 0.5 kg 3-(2-methoxy-5-methylphenyl) -3-phenyl propionic acid in 2.0 L tetrahydrofuran was added drop wise in the suspension of 0.105 kg sodium borohydride in 0.5 L tetrahydrofuran within 2 hrs. After completion of addition, reaction mixture was stirred at RT for 2 hrs. 0.177 kg methanesulfonic acid was added drop wise within 1 hrs. After completion of addition, reaction mixture was stirred at RT for 1 hr. The reaction mixture was stirred at 65-7O0C for 8-10 hrs. After completion of reaction, reaction mixture was cooled at 0-50C. The reaction mixture was acidified with 0.25 L IM aq. HCl up to pH 2-3, and then reaction mixture was extracted with ethyl acetate (1 L x 2). The organic layers were washed with 2.0 L water & 2.0 L brine. The solvent was distilled out to dryness at reduced pressure (30-40 mm Hg) to obtain 3-(2-methoxy-5-methylphenyl)-3-phenyl propanol (Yield: 0.462 kg, 97%)[167] HPLC Purity > 95%.
85%		Example 2 [158] Preparation of 3-(2-methoxy-5-methylphenyl)-3-phenyl propanol; [159](III) (IV) [161] [162] A solution of 0.5 kg of 3-(2-methoxy-5-methylphenyl)-3-phenyl propionic acid in 1.5 L tetrahydrofuran was added drop wise in the suspension of 0.105 Kg of sodium borohydride in 1 L ml tetrahydrofuran under stirring within 2-4 hrs. After completion of addition, reaction mixture was stirred at RT for 2 hrs. 0.181 Kg of Cone. Sulfuric acid was added drop wise within 2-3 hrs. After completion of addition, reaction mixture was stirred at RT for 1-2 hr. The reaction mixture was stirred at 65-7O0C for 6-10 hrs. After completion of reaction, reaction mixture was cooled to 25-3O0C. Saturated brine solution was added to reaction mass and the solution was stirred for 15 min. The organic layer was separated out and distilled it completely. The reaction mass was mixed with aqueous layer and then extracted with dichloromethane (IL x 2). The organic layers were combined and washed with 1 L water &; 1 L brine. The solvent was distilled out to dryness at reduced pressure (30-40 mm Hg) to obtain 3 - (2-methoxy- 5 -methylphenyl) -3 -phenyl propanol.[163] (Yield 0402 Kg, 85%) [164] HPLC Purity >; 96%

Reference： [1]Patent: WO2010/46801,2010,A2 .Location in patent: Page/Page column 16
[2]Patent: WO2010/92500,2010,A2 .Location in patent: Paragraph 157-164

9
[ 124937-73-1 ]
[ 124936-74-9 ]

Reference： [1]Patent: US2012/41235,2012,A1

10
[ 124937-73-1 ]
[ 1161940-88-0 ]

Reference： [1]Patent: US2012/41235,2012,A1

11
[ 40546-94-9 ]
[ 124937-73-1 ]

Reference： [1]Patent: US2012/41235,2012,A1

12
[ 124937-73-1 ]
[ 1043911-42-7 ]

Reference： [1]Patent: US2012/41235,2012,A1

13
1-methoxy-4-methyl-2-(1-phenylallyl)benzene [ No CAS ]
[ 124937-73-1 ]

Reference： [1]Organic Letters,2016,vol. 18,p. 252 - 255

14
[ 7083-19-4 ]
[ 124937-73-1 ]

Reference： [1]Organic Letters,2016,vol. 18,p. 252 - 255

15
(E)-2-(3-bromoprop-1-enyl)-1-methoxy-4-methylbenzene [ No CAS ]
[ 124937-73-1 ]

Reference： [1]Organic Letters,2016,vol. 18,p. 252 - 255

16
[ 50-00-0 ]
[ 389068-20-6 ]
[ 124937-73-1 ]

Reference： [1]Angewandte Chemie - International Edition,2016,vol. 55,p. 6315 - 6318
Angew. Chem.,2016,vol. 128,p. 6423 - 6426,4

17
[ 124937-73-1 ]
C₂₄H₃₅NO [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2016,vol. 55,p. 6315 - 6318
Angew. Chem.,2016,vol. 128,p. 6423 - 6426,4

18
[ 124937-73-1 ]
tolterodine [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2016,vol. 55,p. 6315 - 6318
Angew. Chem.,2016,vol. 128,p. 6423 - 6426,4

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P304 + P312	IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell.
P304 + P340	IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
P304 + P341	IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P305 + P351 + P338	IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P306 + P360	IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes.
P307 + P311	IF exposed: call a POISON CENTER or doctor/physician.
P308 + P313	IF exposed or concerned: Get medical advice/attention.
P309 + P311	IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician.
P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
P337 + P313	IF eye irritation persists: Get medical advice/attention.
P342 + P311	IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician.
P370 + P376	In case of fire: Stop leak if safe to Do so.
P370 + P378	In case of fire:
P370 + P380	In case of fire: Evacuate area.
P370 + P380 + P375	In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion.
P371 + P380 + P375	In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion.
Storage
Code	Phrase
P401
P402	Store in a dry place.
P403	Store in a well-ventilated place.
P404	Store in a closed container.
P405	Store locked up.
P406	Store in corrosive resistant/ container with a resistant inner liner.
P407	Maintain air gap between stacks/pallets.
P410	Protect from sunlight.
P411
P412	Do not expose to temperatures exceeding 50 oC/ 122 oF.
P413
P420	Store away from other materials.
P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
P410 + P403	Protect from sunlight. Store in a well-ventilated place.
P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling

Physical hazards
Code	Phrase
H200	Unstable explosive
H201	Explosive; mass explosion hazard
H202	Explosive; severe projection hazard
H203	Explosive; fire, blast or projection hazard
H204	Fire or projection hazard
H205	May mass explode in fire
H220	Extremely flammable gas
H221	Flammable gas
H222	Extremely flammable aerosol
H223	Flammable aerosol
H224	Extremely flammable liquid and vapour
H225	Highly flammable liquid and vapour
H226	Flammable liquid and vapour
H227	Combustible liquid
H228	Flammable solid
H229	Pressurized container: may burst if heated
H230	May react explosively even in the absence of air
H231	May react explosively even in the absence of air at elevated pressure and/or temperature
H240	Heating may cause an explosion
H241	Heating may cause a fire or explosion
H242	Heating may cause a fire
H250	Catches fire spontaneously if exposed to air
H251	Self-heating; may catch fire
H252	Self-heating in large quantities; may catch fire
H260	In contact with water releases flammable gases which may ignite spontaneously
H261	In contact with water releases flammable gas
H270	May cause or intensify fire; oxidizer
H271	May cause fire or explosion; strong oxidizer
H272	May intensify fire; oxidizer
H280	Contains gas under pressure; may explode if heated
H281	Contains refrigerated gas; may cause cryogenic burns or injury
H290	May be corrosive to metals
Health hazards
Code	Phrase
H300	Fatal if swallowed
H301	Toxic if swallowed
H302	Harmful if swallowed
H303	May be harmful if swallowed
H304	May be fatal if swallowed and enters airways
H305	May be harmful if swallowed and enters airways
H310	Fatal in contact with skin
H311	Toxic in contact with skin
H312	Harmful in contact with skin
H313	May be harmful in contact with skin
H314	Causes severe skin burns and eye damage
H315	Causes skin irritation
H316	Causes mild skin irritation
H317	May cause an allergic skin reaction
H318	Causes serious eye damage
H319	Causes serious eye irritation
H320	Causes eye irritation
H330	Fatal if inhaled
H331	Toxic if inhaled
H332	Harmful if inhaled
H333	May be harmful if inhaled
H334	May cause allergy or asthma symptoms or breathing difficulties if inhaled
H335	May cause respiratory irritation
H336	May cause drowsiness or dizziness
H340	May cause genetic defects
H341	Suspected of causing genetic defects
H350	May cause cancer
H351	Suspected of causing cancer
H360	May damage fertility or the unborn child
H361	Suspected of damaging fertility or the unborn child
H361d	Suspected of damaging the unborn child
H362	May cause harm to breast-fed children
H370	Causes damage to organs
H371	May cause damage to organs
H372	Causes damage to organs through prolonged or repeated exposure
H373	May cause damage to organs through prolonged or repeated exposure
Environmental hazards
Code	Phrase
H400	Very toxic to aquatic life
H401	Toxic to aquatic life
H402	Harmful to aquatic life
H410	Very toxic to aquatic life with long-lasting effects
H411	Toxic to aquatic life with long-lasting effects
H412	Harmful to aquatic life with long-lasting effects
H413	May cause long-lasting harmful effects to aquatic life
H420	Harms public health and the environment by destroying ozone in the upper atmosphere

[ CAS No. 124937-73-1 ] {[proInfo.proName]}

Quality Control of [ 124937-73-1 ]

Related Doc. of [ 124937-73-1 ]

Product Details of [ 124937-73-1 ]

Calculated chemistry of [ 124937-73-1 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 124937-73-1 ]

Application In Synthesis of [ 124937-73-1 ]

[ 124937-73-1 ] Synthesis Path-Upstream 1~5

[ 124937-73-1 ] Synthesis Path-Downstream 1~18

Related Functional Groups of [ 124937-73-1 ]

Aryls

Ethers

Alcohols

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

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[ 124937-73-1 ]