79756-81-3|1-[2-(Trifluoromethyl)phenyl]ethanol| Ambeed

CAS No. :	79756-81-3
Formula :	C₉H₉F₃O
M.W :	190.16
SMILES Code :	CC(O)C1=C(C=CC=C1)C(F)(F)F
MDL No. :	MFCD00004513
InChI Key :	VGHBIJJTMFYTPY-UHFFFAOYSA-N
Pubchem ID :	522725

Safety of [ 79756-81-3 ]

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

Computational Chemistry of [ 79756-81-3 ] Show Less

Physicochemical Properties

Num. heavy atoms	13
Num. arom. heavy atoms	6
Fraction Csp3	0.33
Num. rotatable bonds	2
Num. H-bond acceptors	4.0
Num. H-bond donors	1.0
Molar Refractivity	42.38
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	20.23 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	2.14
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	2.32
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	3.59
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.	2.91
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	2.85
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	2.76

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-2.69
Solubility	0.388 mg/ml ; 0.00204 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.	-2.38
Solubility	0.786 mg/ml ; 0.00414 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	-3.15
Solubility	0.136 mg/ml ; 0.000713 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	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	No
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.	-5.81 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	2.0
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)	1.83

Application In Synthesis of [ 79756-81-3 ]

* 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 [ 79756-81-3 ]

[ 79756-81-3 ] Synthesis Path-Downstream 1~54

1
[ 85-44-9 ]
[ 79756-81-3 ]
[ 127733-45-3 ]

References: [1]Journal of the American Chemical Society,1990,vol. 112,p. 5741 - 5747.

2
[ 447-61-0 ]
[ 75-16-1 ]
[ 79756-81-3 ]

References: [1]Journal of the American Chemical Society,1990,vol. 112,p. 5741 - 5747.

3
[ 79756-81-3 ]
[ 395-45-9 ]

References: [1]Journal of Chemical Research, Miniprint,1981,p. 3216 - 3245.
[2]Journal of the American Chemical Society,1963,vol. 85,p. 3492 - 3496.
[3]Polymer,2011,vol. 52,p. 949 - 953.

4
[ 392-83-6 ]
[ 75-07-0 ]
[ 79756-81-3 ]

References: [1]Journal of Chemical Research, Miniprint,1981,p. 3216 - 3245.
[2]Polymer,2011,vol. 52,p. 949 - 953.

5
[ 75-07-0 ]
[ 3796-19-8 ]
[ 79756-81-3 ]

References: [1]Journal of the American Chemical Society,1963,vol. 85,p. 3492 - 3496.

6
[ 108-22-5 ]
[ 79756-81-3 ]
(S)-1-(2-(trifluoromethyl)phenyl)ethyl acetate [ No CAS ]
(R)-1-(2-(trifluoromethyl)phenyl)ethyl acetate [ No CAS ]

References: [1]Tetrahedron Asymmetry,1996,vol. 7,p. 1581 - 1584.
[2]Tetrahedron Asymmetry,1996,vol. 7,p. 3285 - 3294.

7
[ 5381-99-7 ]
[ 79756-81-3 ]
[ 100-52-7 ]
(Hydroxy-phenyl-methyl)-phosphonic acid mono-[1-(2-trifluoromethyl-phenyl)-ethyl] ester [ No CAS ]

References: [1]Tetrahedron Letters,1996,vol. 37,p. 6073 - 6076.

9
[ 79756-81-3 ]
(S)-1-(2-(trifluoromethyl)phenyl)ethanol [ No CAS ]

References: [1]Tetrahedron Asymmetry,1996,vol. 7,p. 3285 - 3294.
[2]Journal of the American Chemical Society,1990,vol. 112,p. 5741 - 5747.

10
[ 79756-81-3 ]
[ 704-41-6 ]

References: [1]Journal of Chemical Research, Miniprint,1981,p. 3216 - 3245.
[2]Journal of the American Chemical Society,1963,vol. 85,p. 3492 - 3496.

11
[ 79756-81-3 ]
[ 79756-82-4 ]

References: [1]Journal of Chemical Research, Miniprint,1981,p. 3216 - 3245.

12
[ 79756-81-3 ]
(S)-1-(2-trifluoromethylphenyl)ethanol [ No CAS ]

References: [1]Journal of the American Chemical Society,1990,vol. 112,p. 5741 - 5747.

13
[ 79756-81-3 ]
[ 219999-02-7 ]

References: [1]Journal of the American Chemical Society,1963,vol. 85,p. 3492 - 3496.

14
[ 79756-81-3 ]
[ 89380-77-8 ]
[ 929039-94-1 ]

Yield	Reaction Conditions	Operation in experiment
98%		Intermediate Example 1: Methyl 5-amino-3-({(1R)-1-f2-(trifluoromethyl)- phenv?ethylloxy)-2-thiophenecarboxvlate; Step A - Methyl 5-nitro-3-({(1 R)- 1-[2-(trifluoromethyl)phenyl]ethyl}oxy)-2- thiophenecarboxylate; A slurry of polymer-supported triphenylphosphine (62.36 g, 2.21 mmol/g, 137.8 mmol) in DCM (1.0 L) was stirred at room temperature for 10 minutes. The mixture was cooled to 0 0C. Methyl 3-hydroxy-5-nitro-2- thiophenecarboxylate (20.00 g, 98.44 mmol), which may be prepared in a manner analogous to the literature procedure (Barker, J. M.; Huddleston, P. R.; Wood, M. L.; Burkitt, SA Journal of Chemical Research (Miniprint) 200Lambda, 1001-1022) was added, followed by (1 ^-1-[2-(trifluoromethyl)phenyl]ethanol (26.20 g, 137.8 mmol) and di-fe/-butyl azodicarboxylate (31.73 g, 137.8 mmol). The reaction mixture was stirred at room temperature for 21.25 h and then was filtered through a fritted funnel and concentrated. The residue was treated with 4 N HCI in 1 ,4-dioxane (300 ml_) and stirred at room temperature for 3 h. The mixture was then quenched by addition of 3 N sodium hydroxide (300 mL) and saturated aqueous NaHCO3 (200 ml_). The mixture was extracted with DCM (3 x 250 mL). The combined organic fractions were dried over MgSO4, filtered, and concentrated onto silica gel. Purification by column EPO <DP n="41"/>chromatography (0 to 25% EtOAc:hexanes) provided 36.08 g (98%) of the title compound as yellow oil. 1H NMR (300 MHz, CDCI3): delta 7.82 (d, 1H1 J= 7.8 Hz), 7.68 (d, 1 H, J= 7.8 Hz), 7.59 (t, 1H1 J= 7.4 Hz), 7.46 (s, 1 H), 7.42 (t, 1H1 J= 7.6 Hz), 5.77 (q, 1H1 J= 6.1 Hz), 3.94 (s, 3H), 1.74 (d, 3H, J= 6.1 Hz).
98%		Step A-Methyl 5-nitro-3-({(1R)-1-[2-(trifluoromethyl)phenyl]ethyl}oxy)-2-thiophenecarboxylate A slurry of polymer-supported triphenylphosphine (62.4 g, 2.21 mmol/g, 138 mmol) in DCM (1.0 L) was stirred at rt for 10 minutes. The mixture was cooled to 0 C. Methyl 3-iiydroxy-5-nitro-2-thiophenecarboxylate (20.0 g, 98.4 mmol), which may be prepared in a manner analogous to the literature procedure (Barker, J. M.; Huddleston, P. R.; Wood, M. L.; Burkiti, S. A. Journal of Chemical Research (Miniprint) 2001, 1001-1022) was added, followed by (1S)-1-[2-(trifluorcmethyl)phenyl]ethanol (26.2 g, 138 mmol) and di-tert-butyl azodicarboxylate (31.7 g, 138 mmol), The reaction mixture was stirred at rt for 21.25 h and then was filtered through a fritted funnel and concentrated. The residue was treated with 4 N HCl in 1,4-dioxane (300 mL) and stirred at rt for 3 h. The mixture was then quenched by addition of 3 N NaOH (300 mL) and saturated aqueous NaHCO3 (200 mL). The mixture was extracted with DCM (3×250 mL). The combined organic fractions were dried over MgSO4, filtered, and concentrated onto silica gel. Purification by column chromatography (0 to 25% EtOAc:hexanes) provided 36.1 g (98%) of the title compound as yellow oil. 1H NMR (300 MHz, CDCl3): delta 7.82 (d, 1H, J=7.8 Hz), 7.68 (d, 1H, J=7.8 Hz), 7.59 (t 1H, J=7.4 Hz), 7.46 (s, 1H), 7.42 (t, 1H, J=7.6 Hz), 5.77 (q, 1H, J=6.1 Hz), 3.94 (s, 3H), 1.74 (d, 3H, J=6.1 Hz).
98%		INTERMEDIATE EXAMPLE 1; Methyl 5-amino-3-({(1R)-1-[2-(trifluoromethyl)phenyl]ethyl}oxy)-2-thiophenecarboxylate; Step A-Methyl 5-nitro-3-({(1R)-1-[2-(trifluoromethyl)phenyl]ethyl}oxy)-2-thiophenecarboxylate; A slurry of polymer-supported triphenylphosphine (62.36 g, 2.21 mmol/g, 137.8 mmol) in DCM (1.0 L) was stirred at rt for 10 min. The mixture was cooled to 0 C. Methyl 3-hydroxy-5-nitro-2-thiophenecarboxylate (20.00 g, 98.44 mmol), which may be prepared in a manner analogous to the literature procedure (Barker, J. M.; Huddleston, P. R.; Wood, M. L.; Burkitt, S. A. Journal of Chemical Research (Miniprint) 2001, 1001-1022) was added, followed by (1S)-1-[2-(trifluoromethyl)phenyl]ethanol (26.20 g, 137.8 mmol) and di-tert-butyl azodicarboxylate (31.73 g, 137.8 mmol). The reaction mixture was stirred at rt for 21.25 h and then was filtered through a fritted funnel and concentrated. The residue was treated with 4 N HCl in 1,4-dioxane (300 mL) and stirred at rt for 3 h. The mixture was then quenched by addition of 3 N NaOH (300 mL) and saturated aqueous sodium bicarbonate (200 mL). The mixture was extracted with DCM (3×250 mL). The combined organic fractions were dried over MgSO4, filtered, and concentrated onto silica gel. Purification by column chromatography (0 to 25% EtOAc:hexanes) provided 36.08 g (98%) of the title compound as yellow oil. 1H NMR (300 MHz, CDCl3): delta 7.82 (d, 1H, J=7.8 Hz), 7.68 (d, 1H, J=7.8 Hz), 7.59 (t, 1H, J=7.4 Hz), 7.46 (s, 1H), 7.42 (t, 1H, J=7.6 Hz), 5.77 (q, 1H, J=6.1 Hz), 3.94 (s, 3H), 1.74 (d, 3H, J=6.1 Hz).

98%	With di-tert-butyl-diazodicarboxylate; In dichloromethane; at 20℃; for 21.25h;	slurry of polymer-supported triphenylphosphine (62.36 g, 2.21 mmol/g, 137.8 mmol) in DCM (1.0 L) was stirred at room temperature for 10 minutes. The mixture was cooled to 0 0C. Methyl 3-hydroxy-5-nitro-2- thiophenecarboxylate (20.00 g, 98.44 mmol), which may be prepared in a manner analogous to the literature procedure (Barker, J. M.; Huddleston, P. R.; Wood, M. L.; Burkitt, S.A. Journal of Chemical Research (Miniprint) 2Q0Lambda , 1001-1022) was added, followed by (1 S)-1-[2-(trifluoromethyl)phenyl]ethanol (26.20 g, 137.8 mmol) and di-t°/T-butyl azodicarboxylate (31.73 g, 137.8 mmol). The reaction mixture was stirred at room temperature for 21.25 h and then was filtered through a fritted funnel and concentrated. The residue was treated with 4 N HCI in 1,4-dioxane (300 mL) and stirred at room temperature for 3 h. The mixture was then quenched by addition of 3 N sodium hydroxide (300 mL) and saturated aqueous NaHCO3 (200 mL). The mixture was extracted with DCM (3 x 250 mL). The combined organic fractions were dried over MgSO4, filtered, and concentrated onto silica gel. Purification by column chromatography (0 to 25% EtOAc:hexanes) provided 36.08 g (98%) of the title compound as yellow oil. 1H NMR (300 MHz, CDCI3): delta 7.82 (d, 1H, J= EPO <DP n="42"/>7.8 Hz), 7.68 (d, 1 H, J= 7.8 Hz), 7.59 (t, 1 H, J= 7.4 Hz), 7.46 (s, 1 H), 7.42 (t, 1 H, J= 7.6 Hz), 5.77 (q, 1 H, J= 6.1 Hz), 3.94 (s, 3H), 1.74 (d, 3H, J= 6.1 Hz).
98%	With di-tert-butyl-diazodicarboxylate; In dichloromethane; at 0 - 20℃; for 21.25h;	A slurry of polymer-supported triphenylphosphine (62.36 g, 2.21 mmol/g, 137.8 mmol) in dichloromethane (1.0 L) was stirred at room temperature for 10 minutes. The mixture was cooled to 0 C. Methyl 3-hydroxy-5-nitro-2- thiophenecarboxylate (20.00 g, 98.44 mmol), which may be prepared in a manner analogous to the literature procedure (Barker, J. M.; Huddleston, P. R.; Wood, M. L.; Burkitt, S.A. Journal of Chemical Research (Miniprint) 2WLambda , 1001-1022) was added, followed by (1 S)-1-[2-(trifluoromethyl)phenyl]ethanol (26.20 g, 137.8 mmol) and di-terf-butyl azodicarboxylate (31.73 g, 137.8 mmol). The reaction mixture was stirred at room temperature for 21.25 h and then was filtered through a fritted funnel and concentrated. The residue was treated with 4 N HCI in 1 ,4-dioxane (300 ml_) and stirred at room temperature for 3 h. The mixture was then quenched by addition of 3 N sodium hydroxide (300 mL) and saturated aqueous sodium bicarbonate (200 rnL). The mixture was extracted with dichloromethane (3 x 250 mL). The combined organic fractions were dried over magnesium sulfate, filtered, and concentrated onto silica gel. Purification by column chromatography (0 to 25% ethyl acetate:hexanes) provided 36.08 g (98%) of the title compound as yellow oil. 1H NMR (300 MHz, CDCI3): 57.82 (d, 1H, J= 7.8 Hz)1 7.68 (d, 1H, J= 7.8 Hz), 7.59 (t, 1 H, J= 7.4 Hz), 7.46 (s, 1 H), 7.42 (t, 1H, J= 7.6 Hz), 5.77 (q, 1 H, J= 6.1 Hz)1 3.94 (S1 3H)1 1.74 (d, 3H, J= 6.1 Hz).
98%	With triphenylphosphine on polystyrene; di-tert-butyl-diazodicarboxylate; In dichloromethane; at 0 - 20℃; for 21.25h;	Intermediate 29: Methyl delta-ami?o-3-{{{1 ff)-1-\|[2- (trifluoromethyi)phe?yi\|ethyi}oxy)-2-thiophenec3rboxyiateStep A - Methyl 5-nitro-3-({(1/t)-1-(2-(trifluoiOmethyl)phenyl]ethyl}o>cy)-2- thiophenecarboxyiateA slurry of polymer-supported triphenySphosphi?e (82.4 g, 2.21 r?mol/g, 138 r?mol) in DCM (1.0 L) was stirred at for 10 minutes. The mixture was cooled to 0 0G. Methyl 3-hydroxy-5-nitra-2-thiophenecartoxy.ate (20.0 g, 98.4 mmol), which may be prepared in 8 manner analogous to the literature procedure{Barker, J. M.; Huddleston, P. R.; Wood, M.L.; Burkitt, S.A. Journal of Chemical Research (M/nphirintJIQQt, 1001-1022) was added, followed by {1 S)-I-[Z- {trifliioromethyi)phenyl]ethano. (28.2 g, 138 mmol) and di-t°/f butyl azodicarboxylate (31.7 Q3 138 mmoi). The reaction mixture was stirred at it for 21.25 h and then was filtered through a fritted funnel and concentrated. The <n="124"/>residue was treated with 4 N HC. in 1 ,4-dioxa?e (300 ml) and stirred at rt for 3 h, The mixture was then quenched by addition of 3 N NaOH (300 ml_) and saturated aqueous NaHCO3 (200 ml). The mixture was extracted with DCM (3 x 250 rnL). The combined organic fractions were dried over IVIgSO4, filtered, and concentrated onto silica gel Purification by column chromatography (0 to 25% EtOAc:hexanes) provided 36.1 g (98%) of the title compound as yellow oil. 1H NlVIR (300 MHz1 CDCb): 6 7.82 (d, 1H, J= 7.8 Hz), 7.68 (d, I H1 J= 7,8 Hz), 7,59 (t, 1 H1 J^ 7.4 Hz), 7.46 (s, I H), 7.42

References: [1]Patent: WO2007/30359,2007,A1 .Location in patent: Page/Page column 39-40.
[2]Patent: US2008/300247,2008,A1 .Location in patent: Page/Page column 53.
[3]Patent: US2010/56525,2010,A1 .Location in patent: Page/Page column 25-26.
[4]Patent: WO2007/30361,2007,A2 .Location in patent: Page/Page column 40-41.
[5]Patent: WO2007/30366,2007,A1 .Location in patent: Page/Page column 62-63.
[6]Patent: WO2007/143456,2007,A2 .Location in patent: Page/Page column 122-123.

15
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[ 79756-81-3 ]
[ 872181-46-9 ]

Yield	Reaction Conditions	Operation in experiment
99%		Example 94; 5-[1-(2-Trifluoromethylphenyl)-ethoxy]-quinazoline-2,4-diamine; [00287] Step 1; A solution of alpha-methyl-2- (trifluoromethyl)benzyl (750 mg; 3.9 mmol) in dimethylformamide was added to a cooled (0 C) slurry of sodium hydride (156 mg; 3.9 mmol) in dimethylformamide under nitrogen atmosphere. The reaction mixture was slowly warmed to room temperature, and stirred for 45 minutes. In another vessel, a solution of 2,6-difluorobenzonitrile (543 mg, 3.9 mmol) in dimethylfomamide was chilled to 0 C, and activiated anion was added over 20 minutes. Mixture was then stirred 2 hours at room temperature. The reaction mixture was poured on crushed ice-water, stirred, filtered, washed with water and dried to afford 1.2 g of solid (99% yield) of 2-fluoro-6-[1-(2-trifluoromethylphenyl)-ethoxy]- benzonitrile.

References: [1]Patent: WO2005/123724,2005,A1 .Location in patent: Page/Page column 66.
[2]Journal of Medicinal Chemistry,2008,vol. 51,p. 449 - 469.

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[ 395-45-9 ]
[ 79756-81-3 ]
[ 94022-96-5 ]

References: [1]Journal of Fluorine Chemistry,2006,vol. 127,p. 1252 - 1255.

17
[ 79756-81-3 ]
[ 89380-77-8 ]
[ 929039-94-1 ]

References: [1]Tetrahedron Letters,2008,vol. 49,p. 6348 - 6351.

18
[ 1228689-63-1 ]
[ 79756-81-3 ]
[ 1228689-64-2 ]

Yield	Reaction Conditions	Operation in experiment
	With diphenyl phosphoryl azide; triethylamine; In toluene; at 80℃; for 2h;	Step 2: (4'-{3-Methyl-4-[1-(2-trifluoromethyl-phenyl)-ethoxycarbonylamino]-isoxazol-5-yl}-biphenyl-4-yl)-acetic acid ethyl ester5-(4'-Ethoxycarbonylmethyl-biphenyl-4-yl)-3-methyl-isoxazole-4-carboxylic acid (0.150 g, 0.41 mmol), alpha-methyl-2-trifluoromethylbenzyl alcohol (0.094 g, 0.49 mmol), diphenylphosphoryl azide (0.11 mL, 0.49 mmol), and triethylamine (0.11 mL, 0.49 mmol) were combined in toluene (3 mL) and stirred at 80 C. for 2 hours. After cooling, the mixture was worked-up to give the title compound.

References: [1]Patent: US2010/152257,2010,A1 .Location in patent: Page/Page column 18.

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[ 79756-81-3 ]
[ 1276687-72-9 ]