851789-43-0|2-(3-Hydroxy-1-phenylpropyl)-4-methylphenol| Ambeed

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Quality Control of [ 851789-43-0 ] Purity: 95% SDS Specification

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Product Details of [ 851789-43-0 ]

CAS No. :	851789-43-0
Formula :	C₁₆H₁₈O₂
M.W :	242.31
SMILES Code :	CC1=CC(C(CCO)C2=CC=CC=C2)=C(O)C=C1
MDL No. :	MFCD11100714
InChI Key :	MJPIYYRDVSLOME-UHFFFAOYSA-N
Pubchem ID :	11481905

Safety of [ 851789-43-0 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H302-H315-H319-H335
Precautionary Statements:	P261-P305+P351+P338

Computational Chemistry of [ 851789-43-0 ] Show Less

Physicochemical Properties

Num. heavy atoms	18
Num. arom. heavy atoms	12
Fraction Csp3	0.25
Num. rotatable bonds	4
Num. H-bond acceptors	2.0
Num. H-bond donors	2.0
Molar Refractivity	73.66
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	40.46 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	2.55
Log P_o/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry	3.32
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	3.21
Log P_o/w (MLOGP)? MLOGP: Topological method implemented from Moriguchi I. et al. 1992 Chem. Pharm. Bull. Moriguchi I. et al. 1994 Chem. Pharm. Bull. Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.	3.19
Log P_o/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	3.81
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	3.22

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-3.66
Solubility	0.0526 mg/ml ; 0.000217 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble
Log S (Ali)? Ali: Topological method implemented from Ali J. et al. 2012 J. Chem. Inf. Model.	-3.85
Solubility	0.0345 mg/ml ; 0.000143 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	-5.02
Solubility	0.00234 mg/ml ; 0.00000964 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Moderately soluble

Pharmacokinetics

GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg	High
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg	Yes
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) and tested on 415 molecules (test set) 10-fold CV: ACC=0.72 / AUC=0.77 External: ACC=0.88 / AUC=0.94	No
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.83 / AUC=0.90 External: ACC=0.84 / AUC=0.91	No
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.80 / AUC=0.86 External: ACC=0.80 / AUC=0.87	No
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) and tested on 2075 molecules (test set) 10-fold CV: ACC=0.78 / AUC=0.85 External: ACC=0.71 / AUC=0.81	No
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) and tested on 1068 molecules (test set) 10-fold CV: ACC=0.79 / AUC=0.85 External: ACC=0.81 / AUC=0.87	Yes
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) and tested on 2579 molecules (test set) 10-fold CV: ACC=0.77 / AUC=0.85 External: ACC=0.78 / AUC=0.86	No
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from Potts RO and Guy RH. 1992 Pharm. Res.	-5.42 cm/s

Druglikeness

Lipinski? Lipinski (Pfizer) filter: implemented from Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev. MW ≤ 500 MLOGP ≤ 4.15 N or O ≤ 10 NH or OH ≤ 5	0.0
Ghose? Ghose filter: implemented from Ghose AK. et al. 1999 J. Comb. Chem. 160 ≤ MW ≤ 480 -0.4 ≤ WLOGP ≤ 5.6 40 ≤ MR ≤ 130 20 ≤ atoms ≤ 70	None
Veber? Veber (GSK) filter: implemented from Veber DF. et al. 2002 J. Med. Chem. Rotatable bonds ≤ 10 TPSA ≤ 140	0.0
Egan? Egan (Pharmacia) filter: implemented from Egan WJ. et al. 2000 J. Med. Chem. WLOGP ≤ 5.88 TPSA ≤ 131.6	0.0
Muegge? Muegge (Bayer) filter: implemented from Muegge I. et al. 2001 J. Med. Chem. 200 ≤ MW ≤ 600 -2 ≤ XLOGP ≤ 5 TPSA ≤ 150 Num. rings ≤ 7 Num. carbon > 4 Num. heteroatoms > 1 Num. rotatable bonds ≤ 15 H-bond acc. ≤ 10 H-bond don. ≤ 5	0.0
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat implemented from Martin YC. 2005 J. Med. Chem.	0.55

Medicinal Chemistry

PAINS? Pan Assay Interference Structures: implemented from Baell JB. & Holloway GA. 2010 J. Med. Chem.	0.0 alert
Brenk? Structural Alert: implemented from Brenk R. et al. 2008 ChemMedChem	0.0 alert: heavy_metal
Leadlikeness? Leadlikeness: implemented from Teague SJ. 1999 Angew. Chem. Int. Ed. 250 ≤ MW ≤ 350 XLOGP ≤ 3.5 Num. rotatable bonds ≤ 7	No; 1 violation:MW<1.0
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties, trained on 12'782'590 molecules and tested on 40 external molecules (r² = 0.94)	2.48

Application In Synthesis of [ 851789-43-0 ]

* 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.

Downstream synthetic route of [ 851789-43-0 ]

[ 851789-43-0 ] Synthesis Path-Downstream 1~35

1
[ 851789-43-0 ]
[ 98-74-8 ]
C₂₂H₂₁NO₆S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide; In tetrahydrofuran; water; at -5 - 20℃; for 2.25h;	Example 1: 2-[3-(p-nitrobenzenesulfonyloxy)-l-phenylpropyl] -4-methyl-(p-nitrobenzenesulfonyloxy)benzene; [55] <strong>[851789-43-0]3-(2-hydroxy-5-methylphenyl)-3-phenylpropanol</strong> (100.0 g), p-nitrobenzenesulfonyl chloride (91.5 g), and tetrahydrofuran (1 L) were introduced into a 2 L three-necked flask equipped with a thermometer. The reaction mixture was stirred at room temperature for about 10 minutes and then maintained at -5 0C or less. A solution of sodium hydroxide (33.01 g) in purified water (66 mL) was added thereto over 15 minutes. The reaction solution was stirred at room temperature for two hours after the addition of the aqueous sodium hydroxide solution was completed. The reaction mixture was concentrated under a reduced pressure. To the resultant concentrate was added methylene chloride (1 L). The resultant solution was twice washed with purified water (500 mL), dried over anhydrous magnesium sulfate, and then filtered.[56] The filtrate, together with p-nitrobenzenesulfonyl chloride (100.6 g), was introduced into a 2 L three-necked flask equipped with a thermometer. The reaction mixture was stirred at room temperature for about 10 minutes and then maintained at -5 0C or less. Triethylamine (83.5 g) was dropwise added thereto over 15 minutes. The reaction solution was stirred at room temperature for two hours after the dropwise addition of triethylamine was completed, twice washed with purified water (500 mL), and then dried over anhydrous magnesium sulfate. The organic phase was concentrated under a reduced pressure and then recrystallized from acetone to give the titled compound (220.0 g, 87percent).[57] 1H NMR(300MHz, CDCl ): 8.35(dd, 4H), 8.04(dd, 4H), 7.22-7.10(m, 3H),7.06-6.84.(m, 5H), 4.3 l(t, IH), 4.15-3.96(m, 2H), 2.27(s, 3H), 2.45-2. l(m, 2H)

References: [1]Patent: WO2007/126217,2007,A1 .Location in patent: Page/Page column 7.
[2]Organic Process Research and Development,2007,vol. 11,p. 918 - 921.

2
[ 851789-43-0 ]
[ 98-59-9 ]
C₂₃H₂₄O₄S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide; In tetrahydrofuran; water; at -5 - 20℃; for 2.25h;	Example 2: 2-[3-(p-nitrobenzenesulfonyloxy)-l-phenylpropyl] -4-methyl-(p-toluenesulfonyloxy)benzene; [59] <strong>[851789-43-0]3-(2-hydroxy-5-methylphenyl)-3-phenylpropanol</strong> (100.0 g), p-toluenesulfonyl chloride (78.7 g), and tetrahydrofuran (1 L) were introduced into a 2 L three-necked <n="9"/>flask equipped with a thermometer. The reaction mixture was stirred at room temperature for about 10 minutes and then maintained at -5 0C or less. A solution of sodium hydroxide (33.0 g) in purified water (66 mL) was added thereto over 15 minutes. The reaction solution was stirred at room temperature for two hours after the addition of the aqueous sodium hydroxide solution was completed. The reaction mixture was concentrated under a reduced pressure. To the resultant concentrate was added methylene chloride (1 L). The resultant solution was twice washed with purified water (500 mL), dried over anhydrous magnesium sulfate, and then filtered.[60] The filtrate, together with p-nitrobenzenesulfonyl chloride (100.6 g), was introduced into a 2 L three-necked flask equipped with a thermometer. The reaction mixture was stirred at room temperature for about 10 minutes and then maintained at -5 0C or less. Triethylamine (83.5 g) was dropwise added thereto over 15 minutes. The reaction solution was stirred at room temperature for two hours after the dropwise addition of triethylamine was completed, twice washed with purified water (500 mL), and then dried over anhydrous magnesium sulfate. The organic phase was concentrated under a reduced pressure and then recrystallized from acetone to give the titled compound (204.03 g, 85percent).[61] 1H NMR(300MHz, CDCl ): 8.32(d, 2H), 8.03(d, 2H), 7.78(d, 2H), 7.36(d, 2H),7.22-6.75(m, 8H), 4.35(t, IH), 4.15-3.96(m, 2H), 2.48(s, 3H), 2.42-2.25(m, 2H) 2.30(s, 3H)

References: [1]Patent: WO2007/126217,2007,A1 .Location in patent: Page/Page column 7-8.
[2]Organic Process Research and Development,2007,vol. 11,p. 918 - 921.

3
[ 16299-22-2 ]
[ 828933-86-4 ]
(S)-6-methyl-4-phenylchroman-2-ol [ No CAS ]
[ 851789-43-0 ]

References: [1]Journal of Organic Chemistry,2007,vol. 72,p. 6056 - 6059.

4
[ 349547-18-8 ]
(S)-6-methyl-4-phenylchroman-2-ol [ No CAS ]
[ 851789-43-0 ]

References: [1]Journal of Organic Chemistry,2007,vol. 72,p. 6056 - 6059.

5
[ 16299-22-2 ]
[ 851789-43-0 ]

References: [1]Journal of Organic Chemistry,2007,vol. 72,p. 6056 - 6059.
[2]Journal of Organic Chemistry,2007,vol. 72,p. 6056 - 6059.

6
[ 851789-43-0 ]
[ 100-44-7 ]
[ 854306-68-6 ]

Yield	Reaction Conditions	Operation in experiment
96%	With sodium hydroxide; tetrabutylammomium bromide; In water; toluene; at 50℃; for 8h;	EXAMPLE 2 Preparation of 3-(2-benzyloxy-5-methylphenyl)-3-phenylpropanol (IV, R=benzyl) 80 ml of an aqueous solution of NaOH (30percent wt./vol.) and 10.6 g (0.033 moles) of tetrabutylammonium bromide (TBABr) were added to a suspension of <strong>[851789-43-0]3-(2-hydroxy-5-methylphenyl)-3-phenylpropanol</strong> of the formula (VIII) (80 g, 0.330 moles) in toluene (320 ml). The internal temperature was adjusted to 50° C., 45.5 ml (0.396 moles) of benzyl chloride were added dropwise in approx. 1 h and the course of the reaction was monitored by means of TLC (eluent: cyclohexane/acetone: 70/30) until the substrate had completely disappeared. After 7 h, the reaction mixture was cooled to ambient temperature and the aqueous phase was removed. The organic phase was washed with water (3*100 ml), was then evaporated under a vacuum to remove the solvent and to obtain 104 g of 3-(2-benzyloxy-5-methylphenyl)-3-phenylpropanol (IV) as a yellow-brown oil (yield 96percent).
	With potassium carbonate; potassium iodide; In acetone; for 42h;Heating / reflux;	Intermediate 7; 3-(2-benzyloxy-5-methyl-phenyl .-3-phenyl-propan-1-ol; Intermediate 6 (75 gms) was dissolved in 750 ml acetone. Anhydrous potassium carbonate (170 gms) and potassium iodide (0.75 gms) were added. 60 ml of benzyl chloride was added slowly and the reaction mixture was refluxed for 42 hours. The reaction mass was cooled to room temperature and filtered. The acetone was concentrated under vacuum. N-hexane 300 ml was added to the oil and stirred for one hour at 20°C. The product was filtered and the solids were dried at 50°C to 55°C in a hot air oven for 3 hours. Yield: 102 gms. (mp 69- 71°C)

References: [1]Patent: US2006/79716,2006,A1 .Location in patent: Page/Page column 7.
[2]Patent: WO2005/61432,2005,A1 .Location in patent: Page/Page column 14.

7
[ 40546-94-9 ]
[ 851789-43-0 ]

Yield	Reaction Conditions	Operation in experiment
97%		A solution of 7-methyl-4-phenyl-3,4-dihydrocoumarin (compound of formula I) (9.52 g, 40.0 mmol) in dry tetrahydrofuran (50 ml) is added drop-wise to the cooled (0 °C) suspension of lithium aluminum hydride (3.04 g, 80 mmol) in 100 ml of dry tetrahydrofuran. The reaction mixture is stirred for 1 hour at room temperature under inert atmosphere and then the reaction is quenched by careful addition of 50 ml of a mixture tetrahydrofuran and water (1 :1) followed by acidification with 1 mol/l solution of hydrochloric acid (150 ml). The product is extracted with ethyl acetate. The combined organic phases are washed with water and brine, and dried over anhydrous magnesium sulphate. After removal of the solvents the compound of formula Il is obtained in 97 percent yield (9.68 g). It is recrystallized from diisopropylether yielding the product as white powder; mp = 112 - 115. 1H NMR (300MHz, DMSO-cfe): delta [ppm] = 2.08 - 2.17 (5H, m, CH3, CH2), 3.29 - 3.31 (2H, m, CH2), 4.38, 4.42 (2H, 2 x t, CH, OH), 6.63 (1 H, d, J = 8.0 Hz, 1 H-Ar), 6.76 (1 H, dd, J = 8.3, 1.7 Hz, 1 H-Ar), 7.00 (1 H, d, J = 1.7Hz, 1 H-Ar), 7.08 - 7.13 (2H, m, 1 H- Ph), 7.20 - 7.28 (3H, m, 4H-Ph), 9.04 (1 H, s, OH)13C NMR (300MHz, DMSO-Of6): delta [ppm] 20.5, 37.6, 39.1, 59.3, 115.0, 125.6, 127.0, 127.3, 127.9, 128.0, 130.9, 145.3, 152.4. ESI mass spectrum: 243 [M + H+]
86%		EXAMPLE 1; Preparation of 3-(2-hydroxy-5-methylphenyl)-3-phenylpropanol (VIII) A basic aqueous solution of sodium borohydride prepared beforehand by dissolving 23.8 g (0.630 moles) of NaBH4 at ambient temperature in 170 ml of H2O and 3.5 ml of 30percent wt./vol. NaOH was added dropwise to a suspension of 3,4-dihydro-6-methyl-4-phenyl-2H-benzopyran-2-one of the formula (II) (100 g, 0.420 moles) in isopropanol (200 ml). Once addition was complete, the temperature was adjusted to 60° C. and the course of the reaction was monitored by TLC (eluent: cyclohexane/acetone: 70/30) until the substrate had completely disappeared. After 5 h, the reaction mixture was cooled to ambient temperature and HCl (2N) was added until a final pH of 7.0 was obtained. Stirring was continued for 30 min at ambient temperature, then the resultant suspension was filtered through a Buchner filter. The filtered solution was concentrated under reduced pressure and the crude residue was crystallised from toluene (280 ml) to yield 87.4 g (yield 86percent) of 3-(2-hydroxy-5-methylphenyl)-3-phenylpropanol (VIII) as a white solid.
70%		Sodium borohydride (0.76 g, 20 mmol) is added in small portions to the cooled solution of 7-methyl-4-phenyl-3,4-dihydrocoumarin (compound of formula I) (0.48 g, 2 mmol) in 20 ml of methanol. The reaction mixture is stirred for 1 h at 0 °C and 4 h at room temperature. The reaction mixture is poured into 1 mol/l solution of hydrochloric acid (120 ml) and extracted with ethyl acetate (3 x 70 ml). The combined organic fractions are dried over anhydrous magnesium sulphate and the solvent evaporated to give the product in 70 percent yield (0.49 g).

Intermediate 6; 2-(3-hydroxy-1-phenyl-propy1 .-4-methyl-phenol; 6-methyl-4-phenyl-chroman-2-one, 250 gms was stirred in 1.25 liters methanol at room temperature. Sodium borohydride 70 gms was added slowly, whilst maintaining the temperature at room temperature. The reaction mixture was stirred for 18 hours. After completion of reaction, the pH of the reaction mass was adjusted to pH 5 using acetic acid. The reaction mixture was concentrated under vacuum and 2 liters of water were added. The reaction mass was stirred for 30 minutes and the solids filtered. The solids were dried at 55°C in a hot air oven for 20 hours. Weight 248 gms. Purification: Crude Intermediate I prepared as above was dissolved in 700 ml of toluene and heated to 85°C-87°C. The clear solution was gradually cooled to room temperature and stirred for 30 minutes. The solids were filtered and washed with toluene. The solids were dried in a hot air oven at 55°C-60°C. Yield: 222 gms. Mp (117-119°C)

References: [1]Patent: WO2006/66931,2006,A1 .Location in patent: Page/Page column 17.
[2]Asian Journal of Chemistry,2014,vol. 26,p. 2813 - 2814.
[3]Tetrahedron Letters,2008,vol. 49,p. 3790 - 3793.
[4]Patent: US2006/79716,2006,A1 .Location in patent: Page/Page column 7.
[5]Journal of Heterocyclic Chemistry,2018,vol. 55,p. 2157 - 2167.
[6]Patent: WO2006/66931,2006,A1 .Location in patent: Page/Page column 17.
[7]Patent: WO2005/61432,2005,A1 .Location in patent: Page/Page column 13-14.
[8]Journal of Heterocyclic Chemistry,2017,vol. 54,p. 653 - 659.

8
[ 851789-43-0 ]
[ 124-63-0 ]
3-(5-methyl-2-((methylsulfonyl)oxy)phenyl)-3-phenylpropyl methansulfonate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
82%	With triethylamine; In dichloromethane; at -5 - 0℃; for 2h;	<strong>[851789-43-0]3-(2-hydroxy-5-methylphenyl)-3-phenylpropanol</strong> (1.15 g, 4.8 mmol) is suspended in 20 ml of dichloromethane and 4.2 ml triethylamine (30 mmol) are added. The solution is cooled to -5 °C and methanesulfonyl chloride (1.55 ml, 20 mmol) is added drop-wise. The reaction mixture is stirred for 2 h at 0 °C and washed with ice-cold water (100 ml), cold 2 mol/l solution of hydrochloric acid (2 x 50 ml) and brine (50 ml). The organic phase is dried over anhydrous magnesium sulphate and solvent evaporated to give yellowish oily residue. After purification with column chromatography using dichloromethane as an eluent the product is obtained in 82 percent yield (1.56 g). EPO <DP n="20"/>1H NMR (300MHz, CDCI3): delta [ppm] = 2.34 (3H, s, CH3), 2.48 (2H, dd, J = 14.4, 6.4Hz, CH2), 2.95, 3.01 (6H, 2 x s, 2 x CH3), 4.17-4.22 (2H, m, CH2), 4.57 (1 H, t, J =7.94 Hz, CH), 7.06 (H, dd, J = 8.3, 2.3 Hz, H-Ar), 7.13 (1 H, d, J = 2.0 Hz, 1 H-Ar),7.21 - 7.36 (6H, m, 5H-Ph, 1 H-Ar).13C NMR (300MHz, CDCI3): delta [ppm] = 21.1 , 34.3, 37.2, 37.9, 39.8, 67.9, 121.6,126.9, 128.0, 128.7, 128.8, 129.2, 135.7, 137.3, 141.8, 145.0ESI mass spectrum: 399 [M + H+]

References: [1]Asian Journal of Chemistry,2014,vol. 26,p. 2813 - 2814.
[2]Patent: WO2006/66931,2006,A1 .Location in patent: Page/Page column 18; 19.
[3]Journal of Heterocyclic Chemistry,2018,vol. 55,p. 2157 - 2167.

9
[ 851789-43-0 ]
[ 594-44-5 ]
[ 894773-88-7 ]

Yield	Reaction Conditions	Operation in experiment
100%	With triethylamine; at 0℃; for 0.25h;	3-(2-Hydroxy-5-methylphenyl)-3-phenylpropanol (4.84 g, 20 mmol) is suspended in 20 ml of dichloromethane. Triethylamine (7.0 ml, 50 mmol) is added and the resulting clear solution is cooled to 0 0C. After the slow addition of ethanesulfonyl chloride (4.2 ml, 44 mmol) the mixture is stirred for 15 minutes at 0 0C. tert-Butyl methyl ether (MTBE, 100 ml) is added. The mixture is washed with 1 mol/l solution of hydrochloric acid (2 x 50 ml), 5 percent solution of sodium hydrogen carbonate (50 EPO <DP n="21"/>ml) and brine (50 ml). The organic phase is dried over anhydrous magnesium sulfate, filtrated and evaporated in vacuo to give the product as a brown oil in quantitative yield (8.5 g).1H NMR (300 MHz, CDCI3): delta [ppm] = 1.37 (3H, t, J = 7.5 Hz, CH2CH3), 1.53 (3H, t, J = 7.5 Hz, CH2CH3), 2.32 (3H1 s, CH3), 2.43 - 2.53 (2H, m, CH2), 3.07 (2H, q, J = 7.5 Hz, CH2CH3), 3.28 (2H, dq, J = 7.5, 1.4 Hz, CH2CH3), 4.22 - 4.37 (2H, m, CH2), 4.60 (1 H, t, J = 7.9 Hz1 CH), 7.02 - 7.07 (1 H, m, 1 H-Ar), 7.09 - 7.13 (1 H, m, 1 H-Ar), 7.19 - 7.35 (6H, m, 1 H-Ar, Ph).

References: [1]Patent: WO2006/66931,2006,A1 .Location in patent: Page/Page column 19; 20.

10
[ 851789-43-0 ]
[ 98-59-9 ]
[ 851789-45-2 ]

Yield	Reaction Conditions	Operation in experiment
85%	With triethylamine; In dichloromethane; at 0 - 20℃; for 4h;	<strong>[851789-43-0]3-(2-hydroxy-5-methylphenyl)-3-phenylpropanol</strong> (1.15 g, 5.0 mmol) is suspended in 20 ml of dichloromethane, 4.20 ml of triethylamine (30 mmol) are added and the mixture is cooled to 0°C. After the addition of p-toluenesulfonylchloride (3.81 g, 20 mmol) the reaction mixture is stirred for 2 h at 0 °C, left to warm up slowly to the room temperature and stirred for additional 2 h. The reaction mixture is washed with ice-cold water (100 ml), cold 2 mol/l solution of hydrochloric acid (2 x 50 ml) and brine (50 ml). The organic phase is dried over anhydrous magnesium sulphate and the solvent evaporated to give oily residue. After purification with column chromatography using a mixture of hexane : ether = 2 : 1 as an eluent the product is obtained in 85 percent yield (2.20 g).1H NMR (300MHz, CDCI3): delta [ppm] = 2.12 - 2.32 (5H, m, CH3, CH2), 2.45, 2.47 (6H, 2 x s, 2 x CH3), 3.79 - 3.98 (2H, m, 2 x CH), 4.20 (1 H, dd, J = 9.2, 6.7 Hz, CH), 6.91 - 7.00 (5H, m, Ph), 7.14 - 7.20 (3H, m, Ar), 7.31 , 7.35 (4H, 2 x d, J = 8.6 Hz, 4H-Ts), 7.73, 7.77 (4H, 2 x d, J = 8.2 Hz, 4H-Ts). 13C NMR (300MHz, CDCI3): delta [ppm] = 21.0, 21.5, 21.6, 33.7, 39.4, 68.3, 121.7, 126.5, 127.8, 128.1 , 128.3, 128.4, 128.6, 129.7, 129.9, 132.7, 132.8, 136.0, 136.9, 141.3, 144.6, 145.2, 145.4. ESI mass spectrum: 551 [M + H+]

References: [1]Patent: WO2006/66931,2006,A1 .Location in patent: Page/Page column 18.
[2]Organic Process Research and Development,2007,vol. 11,p. 918 - 921.

11
[ 851789-43-0 ]
[ 98-09-9 ]
[ 894773-87-6 ]

Yield	Reaction Conditions	Operation in experiment
100%	With 1,4-diaza-bicyclo[2.2.2]octane; In dichloromethane; at 20℃; for 2h;Heating / reflux;	To a well stirred solution of <strong>[851789-43-0]3-(2-hydroxy-5-methylphenyl)-3-phenylpropanol</strong> (4.84 g, 20 mmol) and 1,4-diaza-bicyclo[2.2.2]octane (DABCO, 5.61 g, 50 mmol) in 20 ml of dichloromethane at room temperature benzenesulfonyl chloride (5.6 ml, 44 mmol) is slowly added. The resulting mixture is refluxed for 2 hours. The reaction mixture is then cooled to room temperature and te/t-butyl methyl ether (MTBE, 100 ml) is added. The mixture is washed with 1 mol/l solution of hydrochloric acid (2 x 50 ml), 5 percent solution of sodium hydrogen carbonate (50 ml) and brine (50 ml). The organic phase is dried over anhydrous magnesium sulfate, filtrated and evaporated in vacuo to give the product as a colorless or slightly yellow oil in quantitative yield (10.4 g). 1H NMR (300 MHz, CDCI3): delta [ppm] = 2.12 - 2.36 (2H, m, CH2), 2.25 (3H, s, CH3),3.80 - 3.89 (1 H, m, CH), 3.92 - 4.02 (1 H, m, CH), 4.21 (1 H, dd, J = 9.1 , 6.7 Hz), 6.83 - 7.02 (5H, m, Ph), 7.09 - 7.23 (4H, m, 4H-Ar), 7.47 - 7.73 (6H, m, 6H-Ar),7.81 - 7.99 (3H, m, 3H-Ar).

References: [1]Patent: WO2006/66931,2006,A1 .Location in patent: Page/Page column 19.

12
[ 40546-94-9 ]
[ 108-18-9 ]
[ 851789-43-0 ]
[ 124937-51-5 ]
[ 209747-04-6 ]

Yield	Reaction Conditions	Operation in experiment
		Following procedure similar to that described in patent US-A-5 922 914, a solution of 100 mg (0.42 MMOL) of (IIA), having [a] D20 =-2. 8 (CHC13, c = 1.44) and prepared according to the preceding Example 2, in anhydrous toluene (3 ML), was placed in a 100-MT two-necked flask that had been flamed beforehand. A solution of 1 M. DIBAL in toluene (440 ul, 0.44 MMOL) was added dropwise to this solution, under N2 and AT-25GC. The reaction was monitored by GC-MS and was stopped with 3 ml of ethyl acetate AT-25°C after 5 h, when GC-MS showed there was formation of 6-methyl-4-phenyl-chroman-2-ol at 89percent, together with unreacted starting product (7percent) and a product of further reduction [3- phenyl-3 (2'hydroxy, 5 METHYL) PHENYL-PROPAN-1-OL] (4percent). 3 ml of a 23percent citric acid solution was added. The solution was stirred at room temperature over night. The organic phase was separated and washed with H20, dried over NA2SO4, filtered and the solvent was removed by evaporation at reduced pressure. The raw product thus obtained was placed in a glass cylinder in an autoclave. CH30H (5 ML), Pd/C 5percent (20 mg), (PRI) 2NH (147 LUI, 1.05 MMOL) and H2 were added at 5 atmospheres. The reaction was continued for 12 h at 48°C. The temperature was brought back to room temperature and the autoclave was depressurized by eliminating the gas. After filtration of the catalyst on celite, a GC-MS analysis was carried out, which showed 6-methyl-4-phenyl-chroman-2-ol (2percent), (IIA) 5percent, [3-PHENYL-3 (2 HYDROXY, 5 METHYL) PHENYL-PROPAN-1-OL] (16percent), and (S)- TOLTERODINE (77percent). The raw product was purified by flash chromatography on SI02 (hexane: EtOAc (7: 3) /Et3N 98: 2) to give a colourless oil (100 mg; 73percent); [a] D20 =-23 (c = 1.5 ; CH30H).

References: [1]Patent: WO2005/5356,2005,A2 .Location in patent: Page/Page column 11; 12.

13
[ 106-44-5 ]
[ 4850-49-1 ]
[ 851789-43-0 ]

References: [1]Organic Process Research and Development,2007,vol. 11,p. 918 - 921.

14
[ 851789-43-0 ]
N,N-diisopropyl-3-(2-(p-toluenesulfonyloxy)-5-methylphenyl)-3-phenylpropyl amine [ No CAS ]

References: [1]Organic Process Research and Development,2007,vol. 11,p. 918 - 921.

15
[ 851789-43-0 ]
2-(3-(4-nitrobenzenesulfonyloxy)-1-phenylpropyl)-4-methylphenyl p-nitrobenzenesulfonate [ No CAS ]

References: [1]Organic Process Research and Development,2007,vol. 11,p. 918 - 921.

16
[ 851789-43-0 ]
2-(3-(4-nitrobenzenesulfonyloxy)-1-phenylpropyl)-4-methylphenyl p-toluenesulfonate [ No CAS ]

References: [1]Organic Process Research and Development,2007,vol. 11,p. 918 - 921.

17
[ 851789-43-0 ]
N,N-diisopropyl-3-(2-hydroxy-5-methylphenyl)-3-phenylpropylamine hydrochloride [ No CAS ]

References: [1]Organic Process Research and Development,2007,vol. 11,p. 918 - 921.

18
[ 851789-43-0 ]
[ 124937-52-6 ]

References: [1]Organic Process Research and Development,2007,vol. 11,p. 918 - 921.

19
[ 94-02-0 ]
[ 851789-43-0 ]

References: [1]Organic Process Research and Development,2007,vol. 11,p. 918 - 921.

20
[ 851789-43-0 ]
[ 124936-74-9 ]

References: [1]Asian Journal of Chemistry,2014,vol. 26,p. 2813 - 2814.

21
[ 851789-43-0 ]
2-(3-N,N-diisopropylamino-1-phenylpropyl)-4-methylphenyl methanesulfonate [ No CAS ]

References: [1]Asian Journal of Chemistry,2014,vol. 26,p. 2813 - 2814.

22
[ 106-44-5 ]
[ 851789-43-0 ]

References: [1]Journal of Heterocyclic Chemistry,2017,vol. 54,p. 653 - 659.
[2]Journal of Heterocyclic Chemistry,2018,vol. 55,p. 2157 - 2167.

23
[ 140-10-3 ]
[ 851789-43-0 ]

References: [1]Journal of Heterocyclic Chemistry,2017,vol. 54,p. 653 - 659.
[2]Journal of Heterocyclic Chemistry,2018,vol. 55,p. 2157 - 2167.

24
[ 851789-43-0 ]
[ 770-12-7 ]
8-methyl-2-phenoxy-6-phenyl-5,6-dihydro-4H-1,3,2-benzodioxaphosphocine-2-oxide [ No CAS ]