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[ CAS No. 32858-93-8 ] {[proInfo.proName]}

,{[proInfo.pro_purity]}

Cat. No.: {[proInfo.prAm]}

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2D 3D

Chemical Structure| 32858-93-8

Chemical Structure| 32858-93-8

Structure of 32858-93-8 * Storage: {[proInfo.prStorage]}

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Quality Control of [ 32858-93-8 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 32858-93-8 ]

SDS Specification

Alternatived Products of [ 32858-93-8 ]

Product Details of [ 32858-93-8 ]

CAS No. :	32858-93-8	MDL No. :	MFCD00236324
Formula :	C₇H₅F₃O₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	GQWMNVOVQZIPJC-UHFFFAOYSA-N
M.W :	178.11	Pubchem ID :	2777299
Synonyms :

Calculated chemistry of [ 32858-93-8 ]

Physicochemical Properties

Num. heavy atoms :	12
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.14
Num. rotatable bonds :	2
Num. H-bond acceptors :	5.0
Num. H-bond donors :	1.0
Molar Refractivity :	35.15
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 :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-5.59 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.82
Log Po/w (XLOGP3) :	2.53
Log Po/w (WLOGP) :	3.55
Log Po/w (MLOGP) :	1.64
Log Po/w (SILICOS-IT) :	1.91
Consensus Log Po/w :	2.29

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	1.0
Bioavailability Score :	0.55

Water Solubility

Log S (ESOL) :	-2.78
Solubility :	0.298 mg/ml ; 0.00167 mol/l
Class :	Soluble
Log S (Ali) :	-2.8
Solubility :	0.285 mg/ml ; 0.0016 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-2.45
Solubility :	0.636 mg/ml ; 0.00357 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.58

Safety of [ 32858-93-8 ]

Signal Word:	Danger	Class:	6.1
Precautionary Statements:	P210-P261-P264-P270-P271-P280-P302+P352-P304+P340-P305+P351+P338-P310-P330-P370+P378-P362+P364-P403+P233-P405-P501	UN#:	2810
Hazard Statements:	H227-H301-H313-H315-H318-H335	Packing Group:	Ⅲ
GHS Pictogram:

Application In Synthesis of [ 32858-93-8 ]

* 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 [ 32858-93-8 ]
Downstream synthetic route of [ 32858-93-8 ]

[ 32858-93-8 ] Synthesis Path-Upstream 1~5

1
[ 456-55-3 ]
[ 32858-93-8 ]

Reference： [1] European Journal of Organic Chemistry, 2001, # 4, p. 691 - 695

2
[ 32858-93-8 ]
[ 690264-39-2 ]

Yield	Reaction Conditions	Operation in experiment
91%	With bromine In dichloromethane at -78 - 20℃; for 48 h;	Bromine (1.0 M in CH₂Cl₂, 45 mmol, 45 mL) was added dropwise to 2-trifluoro- methoxyphenol (7.40 g, 41.5 mmol) in CH₂Cl₂ (100 mL) at -78 ⁰C. The mixture was allowed to warm to rt and was stirred for 48 hours. Na₂SO₃ (aq, sat, 100 mL) was added, and the mixture was stirred vigorously until the orange color dissapeared. The mixture was diluted with CH₂Cl₂ (200 mL) and the organic layer collected, washed with brine, dried (Na₂SO₄) and concentrated to afford 9.6 g(91percent) of the sub-title product.
91%	With bromine In dichloromethane at -78 - 20℃; for 48.33 h;	Bromine (1.0 M in CH₂Cl₂, 45 mL, 45 mmol) was added dropwise over 20 min to a solution of 2-trifiuoromethoxyphenol (7.40 g, 41.5 mmol) in CH₂Cl₂ (100 mL) at -78 ⁰C. The mixture was allowed to warm to rt and was stirred at rt for 48 h. Na₂SO₃ (aq, sat, 100 mL) was added and the mixture was stirred vigorously until the orange colour dissapeared. The mixture was diluted with CH₂Cl₂ (200 mL) and the organic layer was washed with brine, dried (Na₂SO₄) and concentrated to afford 9.6 g (91percent) of the sub-title product.
74%	With bromine In dichloromethane at -78 - 20℃;	Bromine (1.55 ml, 30.3 mmol, 1.1 eq.) in DCM (50 ml) was added dropwise to a solution of 2-trifluoromethoxyphenol (5.0 g, 28.1 mmol, 1.0 eq.) in DCM (70 ml) at -78 ⁰C. The reaction mixture was heated to ambient temperature and stirred for a further 48 h. Then a Na₂S₂Os SH₂O (70 ml) solution was added and the mixture was stirred until the orange colour had disappeared. The solution was diluted with DCM (100 ml), the organic phase was washed with brine, dried over sodium sulfate, and the solvent was evaporated under reduced pressure. The purification was carried out by column chromatography (silica gel, eluted with 20percent EtOAc-hexane) to afford 4-bromo-2- (trifluoromethoxy)phenol in 74percent yield.

23%	With bromine; sodium acetate In acetic acid for 1 h;	Preparation 55 4-Bromo-2-trifluoromethoxy-phenol Bromine (449 mg, 2.81 mmol) was added to a solution of 2-(trifluoromethoxy)phenol (500 mg, 2.81 mmol) and sodium acetate (169 mg, 2.81 mmol) in acetic acid (5 mL) and the solution was stirred for 1 hour. The reaction mixture was then diluted with water (30 mL) and extracted with ethyl acetate (2*50 mL). The organic extracts were combined, dried over magnesium sulfate and concentrated in vacuo to give a colourless oil. The oil was purified by column chromatography on silica gel, eluding with pentane:ethyl acetate, 85:15, to afford the title compound as a white solid in 23percent yield. LRMS (APCI⁺): m/z [M+H]⁺ 255/257
6.2 g	With bromine In dichloromethane at -78 - 20℃; for 48 h;	To a solution of 2-(trifluoromethoxy)phenol (5 g, 28.1 mmol) in CH2C12 (50 mL) at -78 °C was added a bromine (1 M in CH2C12; 30.4 mL, 30.4 mmol) drop wise over 20 mm. The reaction was allowed to warm to ambient temperature and stirredfor 48 h. Saturated Na2SO3 (100 mL) solution was added and the reaction mixture was stirred vigorously until disappearance of the orange color was observed. The biphasic mixture was diluted with CH2C12 (50 mL), and the organic layer was separated, washed with brine (50 mL), dried over Na2SO4, and concentrated in vacuum to give phenol B7a (6.2 g,) as a pale yellow solid. ‘H NMR (400 MHz,CDC13) 6.95 (d, J=8.7 Hz, 1 H), 7.33 (dd, J=8.7, 2.3 Hz, 1 H), 7.38 (d, J=8.8 Hz, 1H).

Reference： [1] Journal of Medicinal Chemistry, 2002, vol. 45, # 14, p. 3112 - 3129
[2] Patent: WO2006/77364, 2006, A1, . Location in patent: Page/Page column 88
[3] Patent: WO2006/77367, 2006, A1, . Location in patent: Page/Page column 136
[4] Patent: WO2010/127208, 2010, A1, . Location in patent: Page/Page column 59
[5] Patent: US2005/43300, 2005, A1, . Location in patent: Page/Page column 44
[6] Patent: WO2010/127212, 2010, A1, . Location in patent: Page/Page column 43
[7] Canadian Journal of Chemistry, 2011, vol. 89, # 3, p. 364 - 384
[8] Patent: WO2017/23631, 2017, A1, . Location in patent: Page/Page column 83

3
[ 32858-93-8 ]
[ 690264-39-2 ]

Reference： [1] Patent: US2004/209865, 2004, A1,

4
[ 32858-93-8 ]
[ 690264-39-2 ]
[ 1027269-90-4 ]

Reference： [1] Journal of Medicinal Chemistry, 2002, vol. 45, # 14, p. 3112 - 3129

5
[ 32858-93-8 ]
[ 1036713-42-4 ]

Reference： [1] Tetrahedron Letters, 2008, vol. 49, # 31, p. 4575 - 4578

[ 32858-93-8 ] Synthesis Path-Downstream 1~88

1
[ 32858-93-8 ]
[ 690264-39-2 ]

Yield	Reaction Conditions	Operation in experiment
91%	With bromine; In dichloromethane; at -78 - 20℃; for 48.0h;	Bromine (1.0 M in CH2Cl2, 45 mmol, 45 mL) was added dropwise to 2-trifluoro- methoxyphenol (7.40 g, 41.5 mmol) in CH2Cl2 (100 mL) at -78 0C. The mixture was allowed to warm to rt and was stirred for 48 hours. Na2SO3 (aq, sat, 100 mL) was added, and the mixture was stirred vigorously until the orange color dissapeared. The mixture was diluted with CH2Cl2 (200 mL) and the organic layer collected, washed with brine, dried (Na2SO4) and concentrated to afford 9.6 g(91%) of the sub-title product.
91%	With bromine; In dichloromethane; at -78 - 20℃; for 48.33h;	Bromine (1.0 M in CH2Cl2, 45 mL, 45 mmol) was added dropwise over 20 min to a solution of 2-trifiuoromethoxyphenol (7.40 g, 41.5 mmol) in CH2Cl2 (100 mL) at -78 0C. The mixture was allowed to warm to rt and was stirred at rt for 48 h. Na2SO3 (aq, sat, 100 mL) was added and the mixture was stirred vigorously until the orange colour dissapeared. The mixture was diluted with CH2Cl2 (200 mL) and the organic layer was washed with brine, dried (Na2SO4) and concentrated to afford 9.6 g (91%) of the sub-title product.
74%	With bromine; In dichloromethane; at -78 - 20℃;Product distribution / selectivity;	Bromine (1.55 ml, 30.3 mmol, 1.1 eq.) in DCM (50 ml) was added dropwise to a solution of 2-trifluoromethoxyphenol (5.0 g, 28.1 mmol, 1.0 eq.) in DCM (70 ml) at -78 0C. The reaction mixture was heated to ambient temperature and stirred for a further 48 h. Then a Na2S2Os SH2O (70 ml) solution was added and the mixture was stirred until the orange colour had disappeared. The solution was diluted with DCM (100 ml), the organic phase was washed with brine, dried over sodium sulfate, and the solvent was evaporated under reduced pressure. The purification was carried out by column chromatography (silica gel, eluted with 20% EtOAc-hexane) to afford 4-bromo-2- (trifluoromethoxy)phenol in 74% yield.

23%	With bromine; sodium acetate; In acetic acid; for 1.0h;	Preparation 55 4-Bromo-2-trifluoromethoxy-phenol Bromine (449 mg, 2.81 mmol) was added to a solution of 2-(trifluoromethoxy)phenol (500 mg, 2.81 mmol) and sodium acetate (169 mg, 2.81 mmol) in acetic acid (5 mL) and the solution was stirred for 1 hour. The reaction mixture was then diluted with water (30 mL) and extracted with ethyl acetate (2*50 mL). The organic extracts were combined, dried over magnesium sulfate and concentrated in vacuo to give a colourless oil. The oil was purified by column chromatography on silica gel, eluding with pentane:ethyl acetate, 85:15, to afford the title compound as a white solid in 23% yield. LRMS (APCI+): m/z [M+H]+ 255/257
	With bromine; In dichloromethane; at 0 - 20℃; for 48.0h;	A solution of bromine (3.1 ml, 61.79 mmol) in 200 ml of DCM was added drop- wise to a solution of 2-trifiuoromethoxyphenol (10 g, 56 mmol) in dichloro methane (100 ml) at 0 0C. The mixture was stirred at room temperature for 48 h. The reaction mixture was quenched with saturated aqueous sodium thiosulfate and extracted with DCM twice. The combined organic extracts were washed with water and brine, dried over anhydrous sodium sulfate, and evaporated to afford crude 4-bromo-2-trifluoromethoxyphenol which was taken without further purification for next step. 1H-NMR (400 MHz, DMSO-d6) delta 10.468 (s, IH), 7.455 (s, IH), 7.355-7.383 (dd, IH, J=I 1.2 Hz, 2.4 Hz), 6.961-6.983 (d, IH, J=8.8 Hz) ppm.
6.2 g	With bromine; In dichloromethane; at -78 - 20℃; for 48.0h;	To a solution of 2-(trifluoromethoxy)phenol (5 g, 28.1 mmol) in CH2C12 (50 mL) at -78 C was added a bromine (1 M in CH2C12; 30.4 mL, 30.4 mmol) drop wise over 20 mm. The reaction was allowed to warm to ambient temperature and stirredfor 48 h. Saturated Na2SO3 (100 mL) solution was added and the reaction mixture was stirred vigorously until disappearance of the orange color was observed. The biphasic mixture was diluted with CH2C12 (50 mL), and the organic layer was separated, washed with brine (50 mL), dried over Na2SO4, and concentrated in vacuum to give phenol B7a (6.2 g,) as a pale yellow solid. ?H NMR (400 MHz,CDC13) 6.95 (d, J=8.7 Hz, 1 H), 7.33 (dd, J=8.7, 2.3 Hz, 1 H), 7.38 (d, J=8.8 Hz, 1H).

Reference： [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 3112 - 3129
[2]Patent: WO2006/77364,2006,A1 .Location in patent: Page/Page column 88
[3]Patent: WO2006/77367,2006,A1 .Location in patent: Page/Page column 136
[4]Patent: WO2010/127208,2010,A1 .Location in patent: Page/Page column 59
[5]Patent: US2005/43300,2005,A1 .Location in patent: Page/Page column 44
[6]Patent: WO2010/127212,2010,A1 .Location in patent: Page/Page column 43
[7]Canadian Journal of Chemistry,2011,vol. 89,p. 364 - 384
[8]Patent: WO2017/23631,2017,A1 .Location in patent: Page/Page column 83

2
[ 32858-93-8 ]
[ 690264-39-2 ]
[ 1027269-90-4 ]

Reference： [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 3112 - 3129

3
[ 32858-93-8 ]
2-hydroxy-3-(trifluoromethoxy)benzoic acid [ No CAS ]

Reference： [1]Tetrahedron,2005,vol. 61,p. 3393 - 3401
[2]Patent: US2013/158067,2013,A1

4
[ 32858-93-8 ]
3-hydroxy-2-(trifluoromethoxy)benzoic acid [ No CAS ]

Reference： [1]Tetrahedron,2005,vol. 61,p. 3393 - 3401

5
[ 32858-93-8 ]
2-methoxymethoxy-3-trifluoromethoxy-benzoic acid [ No CAS ]

Reference： [1]Tetrahedron,2005,vol. 61,p. 3393 - 3401
[2]Patent: US2013/158067,2013,A1

6
[ 32858-93-8 ]
2-trifluoromethoxy-3-triisopropylsilanyloxy-benzoic acid [ No CAS ]

Reference： [1]Tetrahedron,2005,vol. 61,p. 3393 - 3401

7
[ 32858-93-8 ]
2-methoxy-3-(trifluoromethoxy)benzoic acid [ No CAS ]

Reference： [1]Chemistry - A European Journal,2002,vol. 8,p. 799 - 804

8
[ 32858-93-8 ]
3-methoxy-2-(trifluoromethoxy)benzoic acid [ No CAS ]

Reference： [1]Chemistry - A European Journal,2002,vol. 8,p. 799 - 804

9
[ 32858-93-8 ]
[ 853771-88-7 ]

Reference： [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 3112 - 3129
[2]Journal of Medicinal Chemistry,2002,vol. 45,p. 3112 - 3129

10
[ 32858-93-8 ]
4-methoxy-3-(trifluoromethoxy)-benzoic acid [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 3112 - 3129
[2]Journal of Medicinal Chemistry,2002,vol. 45,p. 3112 - 3129

11
[ 32858-93-8 ]
1-allyloxy-4-bromo-2-trifluoromethoxy-benzene [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 3112 - 3129
[2]Journal of Medicinal Chemistry,2002,vol. 45,p. 3112 - 3129

12
[ 32858-93-8 ]
4-bromo-1-(3-methyl-but-2-enyloxy)-2-trifluoromethoxy-benzene [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 3112 - 3129
[2]Journal of Medicinal Chemistry,2002,vol. 45,p. 3112 - 3129

13
[ 32858-93-8 ]
4-bromo-1-but-3-enyloxy-2-trifluoromethoxy-benzene [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 3112 - 3129
[2]Journal of Medicinal Chemistry,2002,vol. 45,p. 3112 - 3129

14
[ 32858-93-8 ]
4-(3'-butenyloxy)-3-trifluoromethoxybenzoic acid [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 3112 - 3129
[2]Journal of Medicinal Chemistry,2002,vol. 45,p. 3112 - 3129

15
[ 32858-93-8 ]
4-Bromo-1-(3-fluoro-benzyloxy)-2-trifluoromethoxy-benzene [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 3112 - 3129
[2]Journal of Medicinal Chemistry,2002,vol. 45,p. 3112 - 3129

16
[ 32858-93-8 ]
4-(3'-fluorobenzyloxy)-3-trifluoromethoxybenzoic acid [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 3112 - 3129
[2]Journal of Medicinal Chemistry,2002,vol. 45,p. 3112 - 3129

17
[ 32858-93-8 ]
[ 445018-76-8 ]

Reference： [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 3112 - 3129

18
[ 32858-93-8 ]
[ 1026470-39-2 ]

Reference： [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 3112 - 3129

19
[ 32858-93-8 ]
[ 709614-51-7 ]

Reference： [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 3112 - 3129

20
[ 32858-93-8 ]
[ 709619-79-4 ]

Reference： [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 3112 - 3129

21
[ 32858-93-8 ]
[ 647855-31-0 ]

Reference： [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 3112 - 3129
[2]Journal of Medicinal Chemistry,2002,vol. 45,p. 3112 - 3129

22
[ 32858-93-8 ]
4-methoxy-3-propyl-5-trifluoromethoxy-benzoyl chloride [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 3112 - 3129

23
[ 32858-93-8 ]
[ 445019-57-8 ]

Reference： [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 3112 - 3129
[2]Journal of Medicinal Chemistry,2002,vol. 45,p. 3112 - 3129

24
[ 32858-93-8 ]
[ 445018-77-9 ]

Reference： [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 3112 - 3129

25
[ 32858-93-8 ]
(R)-2-(4-Allyloxy-3-trifluoromethoxy-phenyl)-4,5-dihydro-oxazole-4-carboxylic acid methyl ester [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 3112 - 3129
[2]Journal of Medicinal Chemistry,2002,vol. 45,p. 3112 - 3129

26
[ 32858-93-8 ]
2-(4-allyloxy-3-trifluoromethoxy-phenyl)-4,5-dihydro-oxazole-4-carboxylic acid hydroxyamide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 3112 - 3129
[2]Journal of Medicinal Chemistry,2002,vol. 45,p. 3112 - 3129

27
[ 32858-93-8 ]
[ 445018-78-0 ]

Reference： [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 3112 - 3129
[2]Journal of Medicinal Chemistry,2002,vol. 45,p. 3112 - 3129

28
[ 32858-93-8 ]
(R)-2-[4-(3-Methyl-but-2-enyloxy)-3-trifluoromethoxy-phenyl]-4,5-dihydro-oxazole-4-carboxylic acid methyl ester [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 3112 - 3129
[2]Journal of Medicinal Chemistry,2002,vol. 45,p. 3112 - 3129

29
[ 32858-93-8 ]
2-[4-(3-methyl-but-2-enyloxy)-3-trifluoromethoxy-phenyl]-4,5-dihydro-oxazole-4-carboxylic acid hydroxyamide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 3112 - 3129
[2]Journal of Medicinal Chemistry,2002,vol. 45,p. 3112 - 3129

30
[ 32858-93-8 ]
(R)-2-(4-Allyloxy-3-trifluoromethoxy-phenyl)-4,5-dihydro-oxazole-4-carboxylic acid hydroxyamide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 3112 - 3129
[2]Journal of Medicinal Chemistry,2002,vol. 45,p. 3112 - 3129

31
[ 32858-93-8 ]
(S)-2-(4-Methoxy-3-propyl-5-trifluoromethoxy-phenyl)-4,5-dihydro-thiazole-4-carboxylic acid methyl ester [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 3112 - 3129
[2]Journal of Medicinal Chemistry,2002,vol. 45,p. 3112 - 3129

32
[ 32858-93-8 ]
(R)-2-(4-Allyloxy-3-trifluoromethoxy-benzoylamino)-3-hydroxy-propionic acid methyl ester [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 3112 - 3129
[2]Journal of Medicinal Chemistry,2002,vol. 45,p. 3112 - 3129

33
[ 32858-93-8 ]
(R)-2-(4-methoxy-5-propyl-3-trifluoromethoxyphenyl)-4,5-dihydrooxazole-4-carboxylic acid hydroxamide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 3112 - 3129
[2]Journal of Medicinal Chemistry,2002,vol. 45,p. 3112 - 3129

34
[ 32858-93-8 ]
(R)-3-Hydroxy-2-[4-(3-methyl-but-2-enyloxy)-3-trifluoromethoxy-benzoylamino]-propionic acid methyl ester [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 3112 - 3129
[2]Journal of Medicinal Chemistry,2002,vol. 45,p. 3112 - 3129

35
[ 32858-93-8 ]
(R)-3-Hydroxy-2-(4-methoxy-3-propyl-5-trifluoromethoxy-benzoylamino)-propionic acid [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 3112 - 3129
[2]Journal of Medicinal Chemistry,2002,vol. 45,p. 3112 - 3129

36
[ 32858-93-8 ]
4-allyloxy-<i>N</i>-(2-hydroxy-1-hydroxycarbamoyl-ethyl)-3-trifluoromethoxy-benzamide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 3112 - 3129
[2]Journal of Medicinal Chemistry,2002,vol. 45,p. 3112 - 3129

37
[ 32858-93-8 ]
4-allyloxy-<i>N</i>-(2-hydroxy-1-hydroxycarbamoyl-ethyl)-3-trifluoromethoxy-benzamide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 3112 - 3129
[2]Journal of Medicinal Chemistry,2002,vol. 45,p. 3112 - 3129

38
[ 32858-93-8 ]
[ 709630-93-3 ]

Reference： [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 3112 - 3129
[2]Journal of Medicinal Chemistry,2002,vol. 45,p. 3112 - 3129

39
[ 32858-93-8 ]
<i>N</i>-(2-hydroxy-1-hydroxycarbamoyl-ethyl)-4-methoxy-3-propyl-5-trifluoromethoxy-benzamide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 3112 - 3129
[2]Journal of Medicinal Chemistry,2002,vol. 45,p. 3112 - 3129

40
[ 32858-93-8 ]
(R)-2-(4-Methoxy-3-propyl-5-trifluoromethoxy-phenyl)-4,5-dihydro-oxazole-4-carboxylic acid benzyloxy-amide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 3112 - 3129
[2]Journal of Medicinal Chemistry,2002,vol. 45,p. 3112 - 3129

41
[ 32858-93-8 ]
(R)-2-(4-Allyloxy-3-trifluoromethoxy-phenyl)-4,5-dihydro-oxazole-4-carboxylic acid (4-methoxy-benzyloxy)-amide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 3112 - 3129
[2]Journal of Medicinal Chemistry,2002,vol. 45,p. 3112 - 3129

42
[ 32858-93-8 ]
<i>N</i>-(1-benzyloxycarbamoyl-2-hydroxy-ethyl)-4-methoxy-3-propyl-5-trifluoromethoxy-benzamide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 3112 - 3129
[2]Journal of Medicinal Chemistry,2002,vol. 45,p. 3112 - 3129

43
[ 50893-53-3 ]
[ 32858-93-8 ]
carbonic acid 1-chloro-ethyl ester 4-trifluoromethoxy-phenyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90%	With triethylamine; In dichloromethane; at 0 - 20℃; for 3h;	Scheme 1. A solution of 1-chloroethyl CHLOROFORMATE (1.03 g; 7.20 MMOL) in CH2CI2 (10 mL) was cooled to 0 C, TRIFLUOROMETHOXYPHENOL (1.09 g; 6.0 MMOL) and triethylamine were added, and the resulting solution was warmed to RT. After stirred for3 h, the reaction was quenched with saturated NAHC03, and extracted with EtOAc (3 times). The combined organic extracts were washed with water, brine, dried over NA2SO4, and the solvent was removed under reduced pressure. The crude residue was purified by flash chromatography eluting with Hexane-EtOAc (10: 1) to provide 1.54 g (90%) of carbonic acid 1- chloro-ethyl ester 4-trifluoromethoxy-phenyl ester as a colorless oil. 1H NMR (400 MHz, CDCI3) : 8 7.26 (m, 4 H), 6.49 (q, 1H), 1.91 (d, 3H)

Reference： [1]Patent: WO2004/37777,2004,A1 .Location in patent: Page 71

44
[ 32858-93-8 ]
[ 106-96-7 ]
[ 352314-76-2 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; In toluene; acetonitrile; at 20℃; for 48h;	Example 46; N-1H-indazol-4-yl-N'-[8-(trifluoromethoxy)-3,4-dihydro-2H-chromen-4-yl]urea; Example 46A; 2-Trifluoromethoxyphenol (5.0 g, 28 mmol), propargyl bromide (4 ml of 80% in toluene, 36 mmol), and potassium carbonate (4.97 g, 36 mmol) were stirred together in 70 ml of acetonitrile at ambient temperature for 2 days. The solvent was removed under reduced pressure, and the residue taken in water and extracted with diethyl ether. The organic layers were combined, dried with magnesium sulfate, and filtered. The solvent was evaporated under reduced pressure to give 5.60 g of Example 46A which was used without further purification.
	With potassium carbonate; In toluene; acetonitrile; at 20℃; for 168h;	To a solution of <strong>[32858-93-8]2-trifluoromethoxyphenol</strong> (10.0 g, 56.1 mmol) in acetonitrile (120 niL) was added potassium carbonate (9.31 g, 67.4 mmol) and propargyl bromide (80% in toluene, 10.0 g, 7.70 mL, 67.4 mmol). The reaction was stirred at ambient temperature for seven days, then diluted with water (150 mL) and extracted with diethyl ether (300 mL). The organic layer was separated and concentrated to obtain the title compound (13.05 g) which was used without further purification in the next step. 1H NMR (300 MHz, CDCl3) delta 7.30- 7.23 (m, 2 H), 7.19-7.13 (m, 1 H), 7.04-6.95 (m, 1 H), 4.77 (d, J=2.4 Hz, 2 H), 2.53 (t, J=2.4 Hz, 1 H).
	With potassium carbonate; In toluene; acetonitrile; at 20℃; for 168h;	To a solution of <strong>[32858-93-8]2-trifluoromethoxyphenol</strong> (10.0 g, 56.1 mmol) in acetonitrile (120 niL) was added potassium carbonate (9.31 g, 67.4 mmol) and propargyl bromide (80% in toluene, 10.0 g, 7.70 mL, 67.4 mmol). The reaction was stirred at ambient temperature for seven days, then diluted with water (150 mL) and extracted with diethyl ether (300 mL). The organic layer was separated and concentrated to obtain the title compound (13.05 g) which was used without further purification in the next step. 1H NMR (300 MHz, CDCl3) delta 7.30- 7.23 (m, 2 H), 7.19-7.13 (m, 1 H), 7.04-6.95 (m, 1 H), 4.77 (d, J=2.4 Hz, 2 H), 2.53 (t, J=2.4 Hz, 1 H).

With potassium carbonate; In toluene; acetonitrile; at 20℃; for 168h;

To a solution of <strong>[32858-93-8]2-trifluoromethoxyphenol</strong> (10.0 g, 56.1 mmol) in acetonitrile (120 mL) was added potassium carbonate (9.31 g, 67.4 mmol) and propargyl bromide (80% in toluene, 10.0 g, 7.70 mL, 67.4 mmol). The reaction mixture was stirred at ambient temperature for seven days, then diluted with water (150 mL) and extracted with diethyl ether (300 mL). The organic layer was separated and concentrated to obtain the title compound (13.05 g) which was used without further purification in the next step.

Reference： [1]Patent: US2006/128689,2006,A1 .Location in patent: Page/Page column 29
[2]Patent: WO2010/45401,2010,A1 .Location in patent: Page/Page column 79-80
[3]Patent: WO2010/45402,2010,A1 .Location in patent: Page/Page column 78
[4]Patent: US2013/158067,2013,A1 .Location in patent: Paragraph 0334

45
[ 32858-93-8 ]
[ 1027269-90-4 ]

Yield	Reaction Conditions	Operation in experiment
	With N-Bromosuccinimide; In N,N-dimethyl-formamide; at 20℃;	The phenol (1.0 g, 5.6 mmol) was dissolved in DMF (28 mL), NBS (2.2 g, 12 mmol) added and the solution stirred at RT overnight. The mixture was diluted with water (100 mL) followed by aqueous/EtOAc work-up to afford the titled compound.

Reference： [1]Patent: WO2007/64553,2007,A2 .Location in patent: Page/Page column 75-76

46
[ 50-00-0 ]
[ 32858-93-8 ]
[ 497959-31-6 ]

Yield	Reaction Conditions	Operation in experiment
41%	With triethylamine; magnesium chloride; In acetonitrile; for 120h;Heating / reflux;	a) 2-Hydroxy-3 -trifluoromethoxybenzaldehyde; A solution of <strong>[32858-93-8]2-trifluoromethoxyphenol</strong> (5.13 g, 28.8 mmol) in anhydrous acetonitrile (150 mL) in oven-dried glassware was treated with triethylamine (15.0 niL, 108 mmol) and MgCl2 (4.11 g, 43.2 mmol) which had been dried under vacuum with heat. Paraformaldehyde (5.18 g, 172 mmol), which had been dried under vacuum with P2O5, was added and the solution was heated to reflux. After 5 days, the reaction was quenched with 1 N HCl (200 mL) and the mixture was extracted using Et2O (2 x 100 mL). The combined organics were washed with brine (2 x 150 mL), dried (Na2SO4) and concentrated to a yellow solid. Purification by column chromatography (silica gel, 98:2 to 95:5 hexanes/EtOAc) gave the title compound (2.45 g, 41%) as a yellow powder: 1H NMR (300 MHz, OMSO-dbeta) delta 10.24 (s, IH), 7.75-7.65 (m, 2H), 7.08 (t, J= 7.9 Hz, IH).; a) 2-Hydroxy-3-trifluoromethoxybenzaldehyde; A solution of <strong>[32858-93-8]2-trifluoromethoxyphenol</strong> (5.13 g, 28.8 mmol) in anhydrous acetonitrile (150 mL) in oven-dried glassware was treated with triethylamine (15.0 niL, 108 mmol) and MgCl2 (4.11 g, 43.2 mmol) which had been dried under vacuum with heating. Paraformaldehyde (5.18 g, 172 mmol), which had been dried under vacuum with P2O5, was then added and the solution was heated to reflux. After 5 days, the reaction was quenched with 1 nu HCl (200 mL). The mixture was extracted using Et2O (2 x 100 mL). The combined organics were washed with brine (2 x 150 mL), dried (Na2SO4) and concentrated to a yellow solid. Purification by column chromatography (silica gel, 98:2 to 95:5 hexanes/EtOAc) gave the title compound (2.45 g, 41%) as a yellow powder: 1H NMR (300MHz, OMSO-d6) delta 10.24 (s, IH), 7.75-7.65 (m, 2H), 7.08 (t, J= 7.9 Hz, IH).

Reference： [1]Patent: WO2007/53131,2007,A2 .Location in patent: Page/Page column 80; 83

47
[ 32858-93-8 ]
[ 109384-19-2 ]
[ 950649-04-4 ]

Yield	Reaction Conditions	Operation in experiment
75%	With di-isopropyl azodicarboxylate; triphenylphosphine; In tetrahydrofuran; at 0 - 20℃;	Step A: 4-(2-Trifluoromethoxy-phenoxy)-piperidine-l-carboxylic acid tert- butyl ester tert-Bnty 4-hydroxy-piperidine- 1 -carboxylic acid (2.26 g, 11.2 mmol), 2- trifluoromethoxyphenol (l.g, 5.61 mmol), diisopropyl azo-dicarboxylate (2.27 g, 11.2 mmol), triphenylphosphine (2.9 g, 11.2) and anhydrous tetrahydrofuran (100 mL) are stirred at 0 0C and allowed to warm to room temperature over night. After the completion of the reaction, the mixture is condensed in vacuo and purified by flash chromatography (ethyl acetate/heptane) to give 4-boc-(2-trifluoromethoxy-phenoxy)- piperidine (1.52 g, 75 %).

Reference： [1]Patent: WO2007/106705,2007,A1 .Location in patent: Page/Page column 98

48
PE [ No CAS ]
[ 32858-93-8 ]
[ 690264-39-2 ]

Yield	Reaction Conditions	Operation in experiment
	With bromine; sodium sulfate; In 4-(dicyanomethylene)-2-methyl-6-(p-dimethylaminostyryl)-4H-pyran; ethyl acetate;	3.6a 4-bromo-2-trifluoromethoxy-phenol 1.55 mL (30.3 mmol) bromine in 50 mL DCM is added dropwise to a solution of 5.0 g (28.1 mmol) 2-trifluoromethoxy-phenol in 70 mL DCM at -78 C. The reaction solution is heated to RT and stirred for a further 48 h. Then 70 mL Na2SO3 solution are added and the mixture is stirred until the orange colour has disappeared. The solution is diluted with DCM, the organic phase is washed with NaCl solution, dried over MgSO4 and the solvent is eliminated i.vac. The purification is carried out by column chromatography on silica gel (gradient: PE to PE:EtOAc 4:1). Yield: 5.36 g (74.3% of theory). C7H4BrF3O2 (M=257.008).

Reference： [1]Patent: US2004/209865,2004,A1

49
[ 32858-93-8 ]
[ 93777-26-5 ]
5-bromo-2-[(trifluoromethoxy)phenoxy]benzaldehyde [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2008,vol. 18,p. 39 - 43

50
[ 32858-93-8 ]
[ 1036713-42-4 ]

Reference： [1]Tetrahedron Letters,2008,vol. 49,p. 4575 - 4578

51
[ 1073488-44-4 ]
[ 32858-93-8 ]
[ 1073488-42-2 ]

Yield	Reaction Conditions	Operation in experiment
78%	With potassium hydroxide; silver nitrate; In N,N-dimethyl-formamide; at 80℃; for 4h;Sealed tube;	[00127] A mixture of compound 4B (30.5 mg, 0.1 mmol), 2-(trifruoromethoxy)- phenol (36 mg, 0.2 mmol), silver nitrate (17 mg, 0.1 mmol) and KOH (8.2 mg, 0.2 mmol) in 1 ml of DMF was heated to 80 0C in a sealed tube for 4 h. At the conclusion of this period, the reaction mixture was cooled to room temperature. Once at the prescribed temperature, 3 ml of brine was added and the resulting mixture was extracted with ethyl acetate (3x5 ml). The organic layer was separated and concentrated in vacuo to yield a residue. The residue was purified by prep HPLC to afford Example 4 as an off-white solid (35 mg, 78%) HPLC Rt (Method A): 3.66 min. LC/MS (m/z) = 447(M+H)+.

Reference： [1]Patent: WO2008/130951,2008,A1 .Location in patent: Page/Page column 67

52
[ 32858-93-8 ]
[ 62-53-3 ]
[ 847872-06-4 ]

Reference： [1]Patent: EP1514865,2005,A1 .Location in patent: Page/Page column 9; 10

53
[ 148148-36-1 ]
[ 32858-93-8 ]
[ 1167435-64-4 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2009,vol. 19,p. 2829 - 2834

54
[ 32858-93-8 ]
[ 7379-35-3 ]
[ 1224466-89-0 ]

Yield	Reaction Conditions	Operation in experiment
		16.7 g of potassium tert-butylate (0.15 mol) were dissolved in 67 g of N,N-dimethylacetamide at room temperature under inert atmosphere. 19.9 g (0.11 mol) of <strong>[32858-93-8]2-trifluoromethoxyphenol</strong> were then added to the stirred solution. The solution was then heated to 140 C., and 11.2 g of chloropyridine hydrochloride (0.075 mol) were added to the reaction mixture in 10 portions at intervals of 30 minutes and stirred for 60 h at 140 C. The reaction solution was cooled to room temperature and admixed with 150 ml of water and 150 ml of methyl tert-butyl ether and adjusted to pH 1 using 37% strength hydrochloric acid. The phases were separated. The aqueous phase was adjusted to pH>11 using 50% strength sodium hydroxide solution and extracted twice with in each case 150 ml of methyl tert-butyl ether. The organic phases were combined. The solvent was removed under reduced pressure. This gave 14.2 g of 4-[2-trifluoromethoxyphenoxy]pyridine (0.057 mol, 75 mol% of theory).

Reference： [1]Patent: US2010/174089,2010,A1 .Location in patent: Page/Page column 4

55
[ 32858-93-8 ]
[ 79-22-1 ]
[ 1233530-99-8 ]

Yield	Reaction Conditions	Operation in experiment
92%	With triethylamine; In dichloromethane; at 0 - 20℃;	2-(Trifluoromethoxy)phenol (6.0 g, 32.7 mmol) was dissolved in methylene chloride and triethylamine (9.1 mL, 65.4 mmol). The mixture was cooled to 0 C. and methyl chloroformate (2.8 mL, 36.0 mmol) was added dropwise. The mixture was stirred for 2 h at room temperature then quenched with saturated NH4Cl. The reaction was diluted with water and the aqueous layer extracted with dichloromethane (2×30 mL). The combined extracts were washed with water (100 mL) and brine (100 mL), dried over MgSO4, filtered and concentrated in vacuo to provide methyl 2-(trifluoromethoxy)phenyl carbonate (7.1 g, 92% yield). 1H NMR (400.0 MHz, DMSO-d6) delta7.36-7.26 (m, 4H), 3.93 (s, 31-1)
	With triethylamine; In dichloromethane; at 25℃; for 2h;	To a cooled solution of <strong>[32858-93-8]2-(trifluoromethoxy)phenol</strong> (0.51 ml, 3.93 mmol) and triethylamine (1.1 ml, 7.86 mmol) in DCM was slowly added methyl chloroformate (0.36 ml, 4.72 mmol) and the reaction was stirred at 25 C. for 2 h. Reaction diluted with DCM and washed with water, brine, dried over anhydrous Na2SO4 and evaporated. The crude cloudy oil (750 mg, 81%) was used in next step without further purification. 1H-NMR (400 MHz, CDCl3) delta ppm 7.30 (m, 4H), 3.93 (s, 3H); 19F-NMR (376.5 MHz, CDCl3) delta ppm -58.10 (s, 3F).
	With triethylamine; In dichloromethane; at 25℃; for 2h;	To a cooled solution of <strong>[32858-93-8]2-(trifluoromethoxy)phenol</strong> (0.51 ml, 3.93 mmol) and triethylamine (1.1 ml, 7.86 mmol) in DCM was slowly added methyl chloroformate (0.36 ml, 4.72 mmol) and the reaction was stirred at 25 C. for 2 h. Reaction diluted with DCM and washed with water, brine, dried over anhydrous Na2SO4 and evaporated. The crude cloudy oil (750 mg, 81%) was used in next step without further purification. 1H-NMR (400 MHz, CDCl3) delta ppm 7.30 (m, 4H), 3.93 (s, 3H); 19F-NMR (376.5 MHz, CDCl3) delta ppm -58.10 (s, 3F).

Reference： [1]Patent: US2010/168094,2010,A1 .Location in patent: Page/Page column 57
[2]Patent: US2019/31655,2019,A1 .Location in patent: Paragraph 0287; 0288
[3]Patent: US2020/39979,2020,A1 .Location in patent: Paragraph 0245

56
[ 56-23-5 ]
[ 32858-93-8 ]
[ 129644-61-7 ]
[ 603-45-2 ]

Reference： [1]Journal of Fluorine Chemistry,2010,vol. 131,p. 1302 - 1307

57
1-methoxy-2-(trifluoromethoxy)benzene [ No CAS ]
[ 32858-93-8 ]
[ 1261609-52-2 ]
[ 90-05-1 ]

Reference： [1]Journal of Fluorine Chemistry,2010,vol. 131,p. 1302 - 1307

58
[ 32858-93-8 ]
[ 79-08-3 ]
[ 1086063-22-0 ]

Yield	Reaction Conditions	Operation in experiment
88%		(55A) [2-(Trifluoromethoxy)phenoxy]acetic acid 2-(Trifluoromethoxy)phenol (1.00 g, 5.61 mmol) was dissolved in dimethylformamide (5 mL), and sodium hydride (63%, 320 mg, 8.40 mmol) was added thereto at 0 C., and then, the resulting mixture was stirred under a nitrogen atmosphere for 10 minutes. Bromoacetic acid (0.95 g, 6.84 mmol) and a dimethylformamide (5 mL) suspension of sodium hydride (63%, 425 mg, 11.2 mmol) were added thereto at room temperature, and the resulting mixture was stirred under a nitrogen atmosphere at room temperature for 6 hours. To the reaction solution, 1 N hydrochloric acid was added, and the organic matter was extracted with ethyl acetate. The organic layer was washed with a saturated sodium chloride solution, then dried over anhydrous sodium sulfate and filtered. Then, the solvent was distilled off under reduced pressure, and the resulting residue was purified by silica gel column chromatography (dichloromethane:methanol=95:5 to 84:16 (v/v)), whereby the objective title compound was obtained as a white solid (1.16 g, yield: 88%). 1H NMR (CDCl3, 500 MHz): delta4.73 (2H, s), 6.96 (1H, dd, J=1.2, 8.2 Hz), 7.05 (1H, m), 7.24-7.31 (2H, m)

Reference： [1]Patent: US2011/53974,2011,A1 .Location in patent: Page/Page column 69

59
[ 32858-93-8 ]
[ 1202577-89-6 ]

Reference： [1]Patent: US2011/53974,2011,A1

60
[ 32858-93-8 ]
[ 1202577-90-9 ]

Reference： [1]Patent: US2011/53974,2011,A1

61
[ 2003-82-9 ]
[ 32858-93-8 ]
[ 352314-76-2 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 1338 - 1341

62
[ 32858-93-8 ]
[ 890839-95-9 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 1338 - 1341
[2]Patent: US2013/158067,2013,A1

63
[ 32858-93-8 ]
[ 5122-99-6 ]
[ 1283146-50-8 ]

Reference： [1]Journal of Medicinal Chemistry,2017,vol. 60,p. 1417 - 1431

64
[ 32858-93-8 ]
[ 1174657-93-2 ]

Reference： [1]Canadian Journal of Chemistry,2011,vol. 89,p. 364 - 384

65
[ 32858-93-8 ]
[ 1174657-94-3 ]

Reference： [1]Canadian Journal of Chemistry,2011,vol. 89,p. 364 - 384

66
[ 32858-93-8 ]
[ 1174657-95-4 ]

Reference： [1]Canadian Journal of Chemistry,2011,vol. 89,p. 364 - 384

67
[ 32858-93-8 ]
[ 1174657-96-5 ]

Reference： [1]Canadian Journal of Chemistry,2011,vol. 89,p. 364 - 384

68
[ 32858-93-8 ]
[ 647856-30-2 ]

Reference： [1]Canadian Journal of Chemistry,2011,vol. 89,p. 364 - 384

69
[ 32858-93-8 ]
[ 1042703-39-8 ]

Reference： [1]Canadian Journal of Chemistry,2011,vol. 89,p. 364 - 384

70
[ 32858-93-8 ]
[ 1174657-92-1 ]

Reference： [1]Canadian Journal of Chemistry,2011,vol. 89,p. 364 - 384

71
[ 32858-93-8 ]
[ 1158733-15-3 ]
(1RS,2RS)-N-tert-butyl-2-((2-trifluoromethoxy)phenoxy)cyclopropanecarboxamide [ No CAS ]
(1SR,2RS)-N-tert-butyl-2-((2-trifluoromethoxy)phenoxy)cyclopropanecarboxamide [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2011,vol. 76,p. 3968 - 3986

72
[ 32858-93-8 ]
[ 141699-55-0 ]
[ 1332300-75-0 ]

Yield	Reaction Conditions	Operation in experiment
	With triphenylphosphine; diethylazodicarboxylate; In tetrahydrofuran; at 20℃; for 48h;Sealed tube;	Step 1A stock solution was made of N-Boc-3-hydroxyazetidine (532 mg) in THF (0.35M), followed by the addition of PPh3 (808 mg) (or resin bound PPh3) and DEAD (920 mg). An appropriate portion of this stock solution was added to a 2-dram round-bottom vial containing the appropriate phenol. The sealed vials were then shaken at RT for 48 h, then concentrated under reduced pressure.

Reference： [1]Patent: WO2011/103196,2011,A1 .Location in patent: Page/Page column 71

73
[ 32858-93-8 ]
[ 1332300-74-9 ]

Reference： [1]Patent: WO2011/103196,2011,A1

74
[ 32858-93-8 ]
[ 1346176-27-9 ]

Reference： [1]Journal of Medicinal Chemistry,2011,vol. 54,p. 8030 - 8050

75
[ 32858-93-8 ]
[ 1346176-12-2 ]

Reference： [1]Journal of Medicinal Chemistry,2011,vol. 54,p. 8030 - 8050

76
[ 32858-93-8 ]
[ 350-30-1 ]
C₁₃H₇ClF₃NO₄ [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2011,vol. 54,p. 8030 - 8050

77
[ 32858-93-8 ]
[ 869088-57-3 ]

Yield	Reaction Conditions	Operation in experiment
	With copper(II) choride dihydrate; lithium chloride; In N,N-dimethyl-formamide; at 100℃; for 72h;	A solution of copper(II)chloride dihydrate (37.2 mmol, 6.34 g) and lithium chloride (18.6 mmol, 788 mg) in DMF (60 mL) was heated to 80 C. before the addition of <strong>[32858-93-8]2-(trifluoromethoxy)phenol</strong> (18.6 mmol, 4 g) dropwise. The reaction was stirred at 100 C. for 72 hours. After cooling, the reaction mixture was partitioned between EtOAc (60 mL) and water (120 mL), extracted with EtOAc (60 mL). The organic layer was washed with water (60 mL), dried over MgSO4, filtered and concentrated in vacuo. The crude material was purified by silica gel column chromatography, eluting product with a gradient of 0-100% DCM in heptane to yield the title compound as a waxy solid (637 mg, 10%). This was used in the next step with no further purification.1HNMR (400 MHz, CDCl3): delta 5.34 (s, 1H), 6.91 (d, 1H), 7.10 (dd, 1H), 7.15-7.19 (m, 1H)LCMS Rt=3.05 minutes MS m/z 211 [M-H]-
	With sulfuryl dichloride; In toluene; at 30℃; for 1.5h;Cooling with ice;	1.78 g of <strong>[32858-93-8]o-trifluoromethoxyphenol</strong> was dissolved in 5 mL of toluene, and the mixture was stirred in an ice water bath for 20 min. 1.485 g of sulfonyl chloride was added dropwise to the reaction system within 10 min, which was then stirred for 20 min. The solution was moved to a water bath maintained at 30 C., and allowed to stir at this temperature for 1 h. 200 mL of 5% sodium carbonate aqueous solution and 50 mL of toluene were added to the system, which was then violently vibrated and isolated (pH of water layer was 10 upon determination). The pH of water layer was adjusted to 2 with 2 N of hydrochloric acid aqueous solution. The solution was extracted with 50 mL of toluene once again. The toluene layers were combined, successively washed with 100 mL of water and 100 mL of saturated sodium chloride aqueous solution, dried over 5 g of anh. MgSO4 for 30 min, and concentrated via a rotary evaporator to obtain a white granular solid. MS anion peak (M-H: 213).

Reference： [1]Patent: US2012/10207,2012,A1 .Location in patent: Page/Page column 40
[2]Patent: US2012/309797,2012,A1 .Location in patent: Paragraph 0115

78
[ 32858-93-8 ]
((2RS,4RS)-2-((1H-1,2,4-triazol-1-yl)methyl)-2-(4-chlorophenyl)-1,3-dioxolan-4-yl)methyl 4-methylbenzenesulfonate [ No CAS ]
1-[[4-[(2-trifluoromethoxyphenoxy)methyl]-2-(4-chlorophenyl)-1,3-dioxolan-2-yl]methyl]-1H-1,2,4-triazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
58.2%	With potassium hydroxide; In N,N-dimethyl-formamide; at 50℃;	General procedure: Potassium hydroxide (160 mg, 2.8 mmol) was added to a solution of tosylate 3 (485 mg, 0.78 mmol) and phenol (70 mg, 0.72 mmol) in dry DMF (5 mL), and the reaction mixture was heated at 50C overnight. After cooling to room temperature, the reaction mixture was diluted with water (20 mL) and EtOAc (20 mL), and the organic phase was separated. The aqueous phase was extracted with EtOAc (3 x 20 mL). All of the organic layers were combined, washed with brine (20 mL), dried over anhydrous sodium sulfate, filtered, concentrated, and purified by flash chromatography on silica gel (EtOAc/hexanes = 1:1), affording target compound 7a (178.8 mg, 74.6% yield)

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 1625 - 1628

79
[ 32858-93-8 ]
[ 1373885-71-2 ]

Reference： [1]Journal of Fluorine Chemistry,2012,vol. 137,p. 108 - 112

80
[ 32858-93-8 ]
[ 1373885-75-6 ]

Reference： [1]Journal of Fluorine Chemistry,2012,vol. 137,p. 108 - 112

81
[ 32858-93-8 ]
[ 1373885-76-7 ]

Reference： [1]Journal of Fluorine Chemistry,2012,vol. 137,p. 108 - 112

82
[ 32858-93-8 ]
[ 1380005-85-5 ]
4-prop-2-ynyloxy-3-trifluoromethoxyphenethylamine [ No CAS ]

Reference： [1]Journal of Fluorine Chemistry,2012,vol. 137,p. 108 - 112

83
[ 32858-93-8 ]
C₂₀H₁₇ClF₃NO₄ [ No CAS ]
[ 1373885-77-8 ]

Reference： [1]Journal of Fluorine Chemistry,2012,vol. 137,p. 108 - 112

84
[ 32858-93-8 ]
[ 1373885-77-8 ]

Reference： [1]Journal of Fluorine Chemistry,2012,vol. 137,p. 108 - 112

85
[ 32858-93-8 ]
[ 1373885-78-9 ]

Reference： [1]Journal of Fluorine Chemistry,2012,vol. 137,p. 108 - 112

86
[ 32858-93-8 ]
C₂₀H₁₈F₃NO₄ [ No CAS ]
[ 1373885-78-9 ]

Reference： [1]Journal of Fluorine Chemistry,2012,vol. 137,p. 108 - 112

87
[ 32858-93-8 ]
[ 63485-50-7 ]
(trans)-methyl 3-(2-(trifluoromethoxy)phenoxy)cyclobutanecarboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
21%	With di-isopropyl azodicarboxylate; triphenylphosphine; In tetrahydrofuran; at 0 - 20℃; for 72h;	Triphenylphosphine (504 mg, 1 .92 mmol) was added to a solution of 2- (trifluoromethoxy)phenol (0.21 mL, 1 .6 mmol) in tetrahydrofuran (5 mL). The reaction mixture was cooled to 0 C, and <strong>[63485-50-7](cis)-methyl 3-hydroxycyclobutanecarboxylate</strong> (250 mg, 1 .92 mmol) was added, followed by DIAD (0.37 mL, 1.9 mmol). After 10 mm, the reaction mixture waswarmed to room temperature, stirred for 3 days, and diluted with water and EtOAc. The mixture was partitioned, and the aqueous layer was extracted with EtOAc. The organic layer was washed with water, dried over sodium sulfate, filtered, and concentrated. The residue was purified on silica gel eluting with a 0%-I 00% EtOAc-hexanes gradient to give the title compound(191 mg, 21%). 1H NMR (400 MHz, CD3SOCD3) 3 2.29-2.39 (m, 2 H), 2.64-2.72 (m, 2 H), 3.14-3.22 (m, I H), 3.65 (5, 3 H), 4.88-4.96 (m, I H), 6.99-7.04 (m, 2 H), 7.16-7.26 (m, I H), 7.29-7.36 (m, I H); LC-MS (LC-ES) M-H = 289.

Reference： [1]Patent: WO2018/69863,2018,A1 .Location in patent: Page/Page column 217

88
[ 55934-02-6 ]
[ 32858-93-8 ]
2,3-dichloro-4-{2-(trifluoromethoxy)phenyloxy}pyridine [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2019,vol. 62,p. 1643 - 1656

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Code	Phrase
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H401	Toxic to aquatic life
H402	Harmful to aquatic life
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H412	Harmful to aquatic life with long-lasting effects
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H420	Harms public health and the environment by destroying ozone in the upper atmosphere