[ CAS No. 3038-48-0 ] {[proInfo.proName]}

Name: 3038-48-0|2-(Trifluoromethyl)phenylacetic acid|97%
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Quality Control of [ 3038-48-0 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 3038-48-0 ]

Product Details of [ 3038-48-0 ]

CAS No. :	3038-48-0	MDL No. :	MFCD00004327
Formula :	C₉H₇F₃O₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	TYOCDHCKTWANIR-UHFFFAOYSA-N
M.W :	204.15	Pubchem ID :	594597
Synonyms :

Calculated chemistry of [ 3038-48-0 ]

Physicochemical Properties

Num. heavy atoms :	14
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.22
Num. rotatable bonds :	3
Num. H-bond acceptors :	5.0
Num. H-bond donors :	1.0
Molar Refractivity :	42.99
TPSA :	37.3 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) :	-5.81 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.51
Log Po/w (XLOGP3) :	2.45
Log Po/w (WLOGP) :	3.48
Log Po/w (MLOGP) :	2.7
Log Po/w (SILICOS-IT) :	2.59
Consensus Log Po/w :	2.55

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	0.0
Bioavailability Score :	0.56

Water Solubility

Log S (ESOL) :	-2.77
Solubility :	0.348 mg/ml ; 0.0017 mol/l
Class :	Soluble
Log S (Ali) :	-2.88
Solubility :	0.271 mg/ml ; 0.00133 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-3.07
Solubility :	0.175 mg/ml ; 0.000855 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.59

Safety of [ 3038-48-0 ]

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

Application In Synthesis of [ 3038-48-0 ]

* 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.

Upstream synthesis route of [ 3038-48-0 ]
Downstream synthetic route of [ 3038-48-0 ]

[ 3038-48-0 ] Synthesis Path-Upstream 1~10

1
[ 124-38-9 ]
[ 3038-48-0 ]

Reference： [1] Chemical Science, 2018, vol. 9, # 21, p. 4873 - 4878

2
[ 512787-35-8 ]
[ 3038-48-0 ]

Reference： [1] Tetrahedron, 2002, vol. 58, # 50, p. 9925 - 9932

3
[ 2499-95-8 ]
[ 3038-48-0 ]

Reference： [1] Journal of the American Chemical Society, 2012, vol. 134, # 10, p. 4600 - 4606

4
[ 447-61-0 ]
[ 3038-48-0 ]

Reference： [1] Tetrahedron, 2002, vol. 58, # 50, p. 9925 - 9932

5
[ 262268-62-2 ]
[ 3038-48-0 ]

Reference： [1] Tetrahedron, 2002, vol. 58, # 50, p. 9925 - 9932

6
[ 346-06-5 ]
[ 3038-48-0 ]

Reference： [1] Arzneimittel Forschung, 1965, vol. 15, p. 1251 - 1253

7
[ 395-44-8 ]
[ 3038-48-0 ]

Reference： [1] Arzneimittel Forschung, 1965, vol. 15, p. 1251 - 1253

8
[ 395-47-1 ]
[ 3038-48-0 ]

Reference： [1] Arzneimittel Forschung, 1965, vol. 15, p. 1251 - 1253

9
[ 3038-47-9 ]
[ 3038-48-0 ]

Reference： [1] Arzneimittel Forschung, 1965, vol. 15, p. 1251 - 1253

10
[ 3038-48-0 ]
[ 360-64-5 ]

Reference： [1] Organic Letters, 2014, vol. 16, # 2, p. 624 - 627

[ 3038-48-0 ] Synthesis Path-Downstream 1~88

1
[ 3038-48-0 ]
[ 107-15-3 ]
[ 5496-23-1 ]

Reference： [1]Arzneimittel-Forschung/Drug Research,1965,vol. 15,p. 1251 - 1253

2
[ 3038-47-9 ]
[ 3038-48-0 ]

Reference： [1]Arzneimittel-Forschung/Drug Research,1965,vol. 15,p. 1251 - 1253

3
[ 6294-89-9 ]
[ 64-17-5 ]
[ 3038-48-0 ]
[ 112753-24-9 ]

Reference： [1]Journal of Heterocyclic Chemistry,1987,vol. 24,p. 1 - 7

4
[ 2233-18-3 ]
[ 3038-48-0 ]
[ 127035-79-4 ]

Reference： [1]Journal of Medicinal Chemistry,1990,vol. 33,p. 1892 - 1898

5
[ 3038-48-0 ]
[ 130497-31-3 ]

Yield	Reaction Conditions	Operation in experiment
	With thionyl chloride; N,N-dimethyl-formamide; In dichloromethane; at 20℃; for 4h;	General procedure: To a solution of substituted phenyl acetic acid or naphthylacetic acid (200 mg, 1.1 mmol) in dry DCM (10 ml) was added SOCl2 (128 mg, 1.1 mmol) and DMF (1 drop). The mixture was stirred at room temperature for 4 hours, following which the solvent was removed in vacuo. Dry DCM (10 ml) was added to re-dissolve the residue. After that, the solution was dropwise added into the mixture of 4-methoxybenzyl hydroxylamine (3) (165 mg, 1.1 mmol) and Et3N (223 mg, 2.2 mmol) in DCM (10 ml) and stirred at room temperature for 1h. The reaction mixture was quenched with water (20 ml) and then extracted with DCM (3 x 20ml). The combined organic layers was washed with brine and dried with anhydrous Na2SO4. The solvent was removed in vacuo. The crude product was purified with column chromatography (33% EA/Petroleum ether) to obtain a white solid in yields range from 68 to 88% yield.
	With oxalyl dichloride; N,N-dimethyl-formamide; In tetrahydrofuran; at 0℃; for 0.5h;Inert atmosphere;	General procedure: Compound 1-4 (10 mmol, 2.5 g), ammonium chloride(10 mmol, 532 mg) and Fe (30 mmol, 1.67 g) were placed in adouble-neck flask, and 40 mL of THF and 8mL of H2Owere added tothe flask. The mixture was refluxed under nitrogen for 4 h. Whenthe reaction solution temperature cooled to room temperature,20 mL of H2O was added. The excess of Fe was filtered, and themixture was extracted with EtOAc (3 20 mL). The organic layerwas dried over anhydrous Na2SO4, filtered and concentrated toobtain the intermediate aminofuranone, which was used in thenext reaction without purification. The carboxylic acid (0.75 mmol)was added into a dry double-neck flask, and 5 mL of dry THF wasadded to the flask. N,N-Dimethylformamide (1.50 mmol, 0.15 mL)was added into the solution under nitrogen at 0 C. When thesewere completely dissolved, oxalyl chloride (3.75 mmol) was addedslowly. After 30 min, the solvent and excess oxalyl chloride werethen removed under reduced pressure to obtain an acyl chloride.The acyl chloride was kept dry. 100 mg of the intermediate aminofuranone was added into a dry double-neck flask, and 5 mL of dryTHFwas added to the flask. When these were completely dissolved,dry pyridine (1.06 mmol, 0.01 mL) was added under nitrogen at0 C. The THF solution of an acyl chloride (0.793 mmol) was addedinto the mixture slowly. After 30 min, 20 mL of saturated ammoniumchloride solution was slowly added into the mixture, and themixture was extracted three times with EtOAc (3 x 20 mL). Theorganic layer was dried over anhydrous Na2SO4, filtered andconcentrated to dryness, which was purified through silica gelcolumn (EA: PE 2: 1) to give A-1~A-7.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 2899 - 2903
[2]Journal of Medicinal Chemistry,1991,vol. 34,p. 397 - 403
[3]Journal of Medicinal Chemistry,1992,vol. 35,p. 2040 - 2048
[4]Bioorganic and medicinal chemistry,2003,vol. 11,p. 1521 - 1530
[5]European Journal of Medicinal Chemistry,2008,vol. 43,p. 792 - 799
[6]Bioorganic and Medicinal Chemistry Letters,2015,vol. 25,p. 607 - 610
[7]European Journal of Medicinal Chemistry,2017,vol. 127,p. 187 - 199
[8],2020,vol. 10

6
[ 3038-48-0 ]
[ 108-24-7 ]
[ 21235-67-6 ]

Reference： [1]Journal of Medicinal Chemistry,1986,vol. 29,p. 924 - 939
[2]Archiv der Pharmazie,1992,vol. 325,p. 751 - 760

7
[ 3038-48-0 ]
[ 16382-38-0 ]
3-(1-Methyl-1H-indol-3-yl)-4-(2-trifluoromethyl-phenyl)-furan-2,5-dione [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1992,vol. 35,p. 177 - 184

8
[ 3038-48-0 ]
[ 100-66-3 ]
[ 114583-91-4 ]

Reference： [1]Journal of Medicinal Chemistry,1988,vol. 31,p. 1754 - 1761

9
[ 31603-77-7 ]
[ 3038-48-0 ]
2-amino-3-biphenyl-4-yl-4-fluoro-naphthalene-1-carboxylic acid [ No CAS ]

Reference： [1]Tetrahedron,2001,vol. 57,p. 5321 - 5326

10
[ 19853-10-2 ]
[ 3038-48-0 ]
2-amino-3-biphenyl-2-yl-4-fluoro-naphthalene-1-carboxylic acid [ No CAS ]

Reference： [1]Tetrahedron,2001,vol. 57,p. 5321 - 5326

11
C₁₄₀H₁₆₂ClN₂₁O₄₃ [ No CAS ]
[ 3038-48-0 ]
C₁₄₉H₁₆₇ClF₃N₂₁O₄₄ [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 3077 - 3085

12
[ 14909-79-6 ]
[ 3038-48-0 ]
(1R,2S)/(1S,2R)-2-(4-morpholinyl)cyclohex-1-yl 2-(trifluoromethyl)phenylacetate [ No CAS ]
trans-2-(4-morpholinyl)cyclohex-1-yl 2-(trifluoromethyl)phenylacetate [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 2818 - 2841

13
[ 3038-48-0 ]
<i>N</i>-{3-benzoyl-4-[2-(2-trifluoromethyl-phenyl)-acetylamino]-phenyl}-3-[5-(4-nitro-phenyl)-furan-2-yl]-acrylamide [ No CAS ]

Reference： [1]Bioorganic and medicinal chemistry,2003,vol. 11,p. 1521 - 1530

14
[ 447-61-0 ]
[ 3038-48-0 ]

Reference： [1]Tetrahedron,2002,vol. 58,p. 9925 - 9932

15
[ 262268-62-2 ]
[ 3038-48-0 ]

Reference： [1]Tetrahedron,2002,vol. 58,p. 9925 - 9932

16
[ 3038-48-0 ]
4-fluoro-2-hydroxy-3-(2-trifluoromethyl-phenyl)-naphthalene-1-carboxylic acid ethyl ester [ No CAS ]

Reference： [1]Tetrahedron,2001,vol. 57,p. 5321 - 5326

17
[ 3038-48-0 ]
2-bromo-2-<o-(trifluoromethyl)phenyl>acetic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With N-Bromosuccinimide; dibenzoyl peroxide; In tetrachloromethane; at 80℃; for 12h;Inert atmosphere; UV-irradiation;	General procedure: 2-(3-(trifluoromethyl)phenyl) acetic acid (42s) (1.0 g, 4.89 mmol),benzoyl peroxide (4.6 mg, 0.019 mmol), and N-bromosuccinimide (0.9 g, 4.89 mmol) were added to CCl4 (50 mL) under nitrogen atmosphere and UV irradiation. The mixture was heated to reflux for12 h. The reaction was cooled to rt and the succinimide was removed by filtration. The CCl4 was removed in vacuo and the residue was extracted with DCM (100 mL 3). The organic layer was washed with brine and dried over Na2SO4. The solid was filtered off, and the filtrate was concentrated under reduced pressure to give 0.7 g of 35s (50% yield).

Reference： [1]Journal of Medicinal Chemistry,1992,vol. 35,p. 2040 - 2048
[2]European Journal of Medicinal Chemistry,2018,vol. 152,p. 542 - 559

18
[ 3038-48-0 ]
Bromo-(2-trifluoromethyl-phenyl)-acetyl chloride [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1992,vol. 35,p. 2040 - 2048
[2]European Journal of Medicinal Chemistry,2018,vol. 152,p. 542 - 559

19
[ 3038-48-0 ]
[ 114584-07-5 ]

Reference： [1]Journal of Medicinal Chemistry,1988,vol. 31,p. 1754 - 1761

20
[ 3038-48-0 ]
[ 114583-99-2 ]

Reference： [1]Journal of Medicinal Chemistry,1988,vol. 31,p. 1754 - 1761

21
[ 3038-48-0 ]
[ 114583-94-7 ]

Reference： [1]Journal of Medicinal Chemistry,1988,vol. 31,p. 1754 - 1761

22
[ 3038-48-0 ]
[ 79287-48-2 ]

Reference： [1]Journal of Medicinal Chemistry,1986,vol. 29,p. 924 - 939

23
[ 3038-48-0 ]
[ 125314-08-1 ]

Reference： [1]Journal of Medicinal Chemistry,1992,vol. 35,p. 177 - 184

24
[ 3038-48-0 ]
[ 107986-87-8 ]

Reference： [1]Journal of Heterocyclic Chemistry,1987,vol. 24,p. 1 - 7

25
[ 3038-48-0 ]
C₁₄H₁₄ClF₃N₂O₅ [ No CAS ]

Reference： [1]Journal of Heterocyclic Chemistry,1987,vol. 24,p. 1 - 7

26
[ 3038-48-0 ]
[ 130497-44-8 ]

Reference： [1]Journal of Medicinal Chemistry,1991,vol. 34,p. 397 - 403

27
[ 346-06-5 ]
[ 3038-48-0 ]

Reference： [1]Arzneimittel-Forschung/Drug Research,1965,vol. 15,p. 1251 - 1253

28
[ 395-44-8 ]
[ 3038-48-0 ]

Reference： [1]Arzneimittel-Forschung/Drug Research,1965,vol. 15,p. 1251 - 1253

29
[ 395-47-1 ]
[ 3038-48-0 ]

Reference： [1]Arzneimittel-Forschung/Drug Research,1965,vol. 15,p. 1251 - 1253

30
[ 302523-50-8 ]
[ 3038-48-0 ]
4-[2-[N-methyl-N-(4-isopropoxyphenyl)amino]ethyl]-1-[[2-(trifluoromethyl)phenyl]acetyl]piperidin-4-ol [ No CAS ]

Reference： [1]Patent: EP1182193,2002,A1 .Location in patent: Example 9

31
[ 3038-48-0 ]
(1R,2S)/(1S,2R)-2-(4-morpholinyl)cyclohex-1-yl 2-(trifluoromethyl)phenylacetate [ No CAS ]
trans-2-(4-morpholinyl)cyclohex-1-yl 2-(trifluoromethyl)phenylacetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	toluene-4-sulfonic acid; In toluene; for 48h;Heating / reflux;	(iii) (1S,2R)/(1R,2S)-2-(4-Morpholinyl)cyclohexyl 2-(trifluoromethyl)phenylacetate: A mixture of 2-(4-morpholinyl)cyclohexanol (7.41 g, 40 mmol, step ii), <strong>[3038-48-0]2-(trifluoromethyl)phenylacetic acid</strong> (10.21 g, 49 mmol) and p-toluenesulfonic acid monohydrate (40 mg) in toluene (60 mL) was refluxed in a Dean & Stark apparatus for 48 hours. To the cooled reaction mixture was added saturated sodium bicarbonate aqueous solution (40 mL), the aqueous layer was separated and extracted with ethyl acetate (3 x 50 mL). The combined organic layers were dried over sodium sulfate and the solvent was evaporated in vacuo to yield a mixture of (1S,2R)/(1R,2S)-2-(4-morpholinyl)cyclohexyl 2-(trifluoromethyl)phenylacetate and (1R,2R)/(1S,2S)-2-(4-morpholinyl)cyclohexyl 2-(trifluoromethyl)phenylacetate. Chromatography by dry column of the cis/trans mixture with mixtures of ethyl acetate-hexanes (+ 0.5% isopropylamine v/v) as eluents provided 3.19 g of the crude title I compound contaminated by the starting material 2-(4-morpholinyl)cyclohexanol. The crude product was partitioned between dichloromethane (30 mL) and 0.5M HCl aqueous solution (7 mL). The aqueous layer was separated and further extracted with dichloromethane (2x18 mL). The combined organic layers were dried over sodium sulfate and the solvent was evaporated in vacuo. Recrystallization from a mixture of ethanol-hexanes yielded 2.78 g of the title compound.

Reference： [1]Patent: EP1087934,2004,B1 .Location in patent: Page 29

32
[ 3038-48-0 ]
[ 114800-58-7 ]
6-(2-chlorophenyl)-7,8,9,10-tetrahydro-1-methyl-9-[2-(2-trifluoromethylphenyl)-1-oxoethyl]-4H-pyrido[4',3';4,5]thieno[3,2-f][1,2,4]triazolo[4,3-a]diazepine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
61%	With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In N,N-dimethyl-formamide; at 20℃; for 72h;	Example 32 6-(2-chlorophenyl)-7,8,9,10-tetrahydro-1-methyl-9-[2-(2-trifluoromethylphenyl)-1-oxoethyl]-4H-pyrido[4',3';4,5]thieno[3,2-f][1,2,4]triazolo[4,3-a]diazepine A mixture containing 6-(2-chlorophenyl)-7,8,9,10-tetrahydro-1-methyl-4H-pyrido[4',3';4,5]thieno[3,2-f]1,2,4-triazolo[4,3-a]1,4-diazepine (2.22 g, 0.006 mol), 2-trifluoromethylphenyl acetic acid (1.35 g, 0.0066 mol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (1.26 g, 0.0066 mol) hydrochloride and triethylamine (1 ml, 0.0066 mol) in 40 ml of anhydrous dimethylformamide is agitated at a temperature close to 20 C. for 72 hours. The solvent is evaporated off with a rotary evaporator while entraining it with toluene. The crude reaction product is taken up in 30 ml of dichloromethane, washed with water and the organic phase is dried over magnesium sulphate and concentrated with a rotary evaporator. Then approximately 4 ml of dichloromethane is added to the reaction mixture then ether is added until precipitation. Agitation is carried out for a few minutes then filtering under vacuum while washing the precipitate with ether. The product obtained is dried under vacuum in order to obtain 2 g (61%) of expected compound in the form of a white solid. Melting point: 224-226 C.

Reference： [1]Patent: US7015213,2006,B1 .Location in patent: Page/Page column 23

33
[ 7664-93-9 ]
[ 3038-48-0 ]
methyl 2-(3-(trifluoromethyl)phenyl)acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In methanol;	REFERENCE EXAMPLE 17 Methyl 2-trifluoromethylphenylacetate A solution of 2-trifluoromethylphenylacetic acid (5.0 g) in methanol (30 ml) containing 5 drops of concentrated sulphuric acid was heated at reflux for 2 hours. The reaction mixture was concentrated, diluted with ethyl acetate (100 ml), washed with 1N sodium hydroxide (25 ml) then with brine (25 ml), dried over magnesium sulphate and evaporated to give the title compound (5.04 g) as a colourless oil.
	In methanol;	REFERENCE EXAMPLE 17 Methyl 2-trifluoromethylphenylacetate A solution of 2-trifluoromethylphenylacetic acid (5.0 g) in methanol (30 ml) containing 5 drops of concentrated sulphuric acid was heated at reflux for 2 hours. The reaction mixture was concentrated, diluted with ethyl acetate (100 ml), washed with 1 N sodium hydroxide (25 ml) then with brine (25 ml), dried over magnesium sulphate and evaporated to give the title compound (5.04 g) as a colourless oil.

Reference： [1]Patent: US6048893,2000,A
[2]Patent: US6124343,2000,A

Yield	Reaction Conditions	Operation in experiment
		EXAMPLE 23 Synthesis of sulfamic acid[2-trifluoromethylphenyl(acetyl)]-2,6-bis(1-methylethyl)phenyl ester This compound was prepared in the same manner as for the title compound of Example 1, except that 2,6-diisopropylphenylacetic acid was replaced with 2-trifluoromethylphenylacetic acid, mp 144-149 C.

35
(3ARS,7ARS)-7,7-diphenylperhydroisoindol-4-one hydrochloride [ No CAS ]
[ 3038-48-0 ]
[ 530-62-1 ]
(3ARS,7ARS)-7,7-diphenyl-2-[(2-(trifluoromethyl)phenyl)acetyl]-4-perhydroisoindolone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; In dichloromethane;	EXAMPLE 45 N,N'-Carbonyldiimidazole (1.13 g) is added to a solution of <strong>[3038-48-0]2-(2-(trifluoromethyl)phenyl)acetic acid</strong> (1.42 g) in dry dichloromethane (30 cc), cooled to +5 C. The mixture is stirred for 1 hour 45 minutes at +5 C. and a solution of (3aRS,7aRS)-7,7-diphenyl-4-perhydroisoindolone hydrochloride (2.3 g) and triethylamine (0.98 cc) in dichloromethane (40 cc) is then added. The reaction mixture is stirred at 20 C. for 18 hours, then washed with distilled water (3*50 cc), dried over magnesium sulphate and filtered and the filtrate is concentrated to dryness under reduced pressure (2.7 kPa). The residue is crystallized from acetonitrile (10 cc). The crystals obtained are drained, washed with isopropyl ether (10 cc) and dried. (3aRS,7aRS)-7,7-diphenyl-2-[(2-(trifluoromethyl)phenyl)acetyl]-4-perhydroisoindolone (1.68 g) melting at 207 C. is obtained.

Reference： [1]Patent: US5102667,1992,A

36
[ 3038-48-0 ]
[ 16848-19-4 ]
[ 951775-31-8 ]

Yield	Reaction Conditions	Operation in experiment
	With 4-methyl-morpholine; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; at 0 - 20℃; for 11h;	N-methylmorpholine (0.200 g, 0.772 mmol) was added to a mixture of 1,2;5,6-Di-O-isopropylidene-3-deoxy-3-amino-alpha-D-allofuranoside (0.200 g, 0.772 mmol), 2-trifluoromethylphenylacetic acid (0.189 g, 0.926 mmol), N-hydroxybenzotriazole (0.208 g, 1.544 mmol) in dry dimethylformamide). The reaction mixture was stirred at OC for 1 hour followed by the addition of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.296 g, 1.544 mmol) at the same temperature. The reaction mixture was stirred at room temperature for 10 hours. The mixture was poured into water, extracted with ethyl acetate, washed with water and brine, dried over anhydrous sodium sulphate and concentrated under reduced pressure. The residue thus obtained was purified by column chromatography using 50% ethyl acetate in hexane solvent mixture as an eluent to furnish the title compound. Yield: 0.130g. 1H NMR (CDCl3, 400 MHz):delta 7.28-7.24 (m, 2H, Ar-H), 6.95-6.90 (m, 2H, Ar-H), 5.98-5.83 (brm, 1H, -NH), 5.84 (d, 1H, J = 3.00Hz, -CH), 4.62 (m, 1H, -CH), 4.20-4.05 (m, 3H, 3x-CH), 3.93-3.82 (m, 2H, 2x-CH), 3.65 (s, 2H, -CH2Ph) and 1.48-1.32 (m, 12H, 4x-CH3)
		N-methylmorpholine (0.200 g, 0.772 mmol) was added to a mixture of 1,2;5,6-Di-O isopropylidene-3-deoxy-3-amino-?-D-allofuranoside (0.200 g, 0.772 mmol), 2-trifluoromethylphenylacetic acid (0.189 g, 0.926 mmol), N-hydroxybenzotriazole (0.208 g, 1.544 mmol) in dry dimethylformamide). The reaction mixture was stirred at 0 C. for 1 hour followed by the addition of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.296 g, 1.544 mmol) at the same temperature. The reaction, mixture was stirred at room temperature for 10 hours. The mixture was poured into water, extracted with ethyl acetate, washed with water and brine, dried over anhydrous sodium sulphate and concentrated under reduced pressure. The residue thus obtained was purified by column chromatography using 50% ethyl acetate in hexane solvent mixture as an eluent to furnish the title compound. Yield: 0.130 g. 1H NMR (CDCl3, 400 MHz): delta 7.28-7.24 (m, 2H, Ar-H), 6.95-6.90 (m, 2H, Ar-H), 5.98-5.83 (brm, 1H, -NH), 5.84 (d, 1H, J=3.00 Hz, -CH), 4.62 (m, 1H, -CH), 4.20-4.05 (m, 3H, 3x-CH), 3.93-3.82 (m, 2H, 2x-CH), 3.65 (s, 2H, -CH2Ph) and 1.48-1.32 (m, 12H, 4x-CH3)

Reference： [1]Patent: EP1842855,2007,A2 .Location in patent: Page/Page column 30
[2]Patent: US2008/114031,2008,A1 .Location in patent: Page/Page column 22-23

37
[ 25126-04-9 ]
[ 3038-48-0 ]
[ 1159275-80-5 ]

Reference： [1]Journal of the American Chemical Society,2009,vol. 131,p. 6989 - 6996

38
[ 6940-76-7 ]
[ 3038-48-0 ]
[ 1123193-83-8 ]

Yield	Reaction Conditions	Operation in experiment
		Thionyl chloride (272 mL) was added to a solution of 2- alphafluoromethylphenylacetic acid (1.9 g) in methanol (38 mL), and the reaction solution was stirred at room temperature for three hours. The reaction solution was concentrated under reduced pressure. The resulting residue was diluted with DMF. Sodium hydride (containing 40% of mineral oil, 410 mg) was added under ice-cooling, and the reaction solution was stirred for 10 minutes. The reaction solution was further stirred at room temperature for 30 minutes and then ice-cooled again. l-ChIoro-3-iodopropane (1.02 mL) was added to the reaction mixture, and the reaction solution was stirred at room temperature overnight. Water and ethyl acetate were added to the reaction mixture and the organic layer was separated. The resulting organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The resulting residue was diluted with ethanol (26.6 mL). Hydrazine monohydrate (7.6 mL) was added, and the reaction solution was stirred at room temperature for two hours and then at 60C for further three hours. The reaction mixture was concentrated under reduced pressure. Saturated aqueous sodium bicarbonate and ethyl acetate and were added to the residue, and the organic layer was separated. The resulting organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (carrier: Chromatorex NH; elution solvent: heptane-ethyl acetate system) to obtain 1.68 g of the title compound. The property values of the compound are as follows.
		To a solution of <strong>[3038-48-0][2-(trifluoromethyl)phenyl]acetic acid</strong> (1.90 g, 9.31 mmol) in methanol (38 mL) was added thionyl chloride (2.68 mL, 37.2 mmol) under ice-cooling, and the mixture was stirred for 3 hr. The solvent was evaporated, and the residue was diluted with DMF (30 mL). Sodium hydride (410 mg, 10.3 mmol) was added, and the mixture was stirred for 30 min. 1-Chloro-3-iodopropane (1.02 mL, 9.50 mmol) was added, and the mixture was further stirred for 15 hr. The reaction mixture was diluted with ethyl acetate, washed with water and saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The residue was diluted with ethanol (27 mL), hydrazine monohydrate (7.6 mL) was added, and the mixture was stirred at room temperature for 2 hr, and at 60C for 20 hr. The solvent was evaporated, diluted with ethyl acetate, and washed with saturated aqueous sodium hydrogen carbonate solution and saturated brine. This was dried over anhydrous sodium sulfate and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (methanol/ethyl acetate=0/100 - 15/85), and the obtained solid was washed with IPE to give the title compound as a white solid (910 mg, 38%). 1H NMR (CDCl3) delta:1.79 - 2.11 (3 H, m), 2.16 - 2.30 (1 H, m), 3.54 - 3.79 (2 H, m), 3.98 - 4.15 (1 H, m), 4.60 (2 H, br), 7.24 (1 H, d, J=7.7 Hz), 7.30 - 7.40 (1 H, m), 7.44 - 7.54 (1 H, m), 7.66 (1 H, d, J=8.0 Hz). MS(ESI):259 [M+H]+.

Reference： [1]Patent: WO2010/25197,2010,A1 .Location in patent: Page/Page column 38; 39
[2]Patent: EP2455380,2012,A1 .Location in patent: Page/Page column 47

39
[ 3038-48-0 ]
[ 109-70-6 ]
[ 1213771-64-2 ]

Yield	Reaction Conditions	Operation in experiment
98%		A IL, 3-necked round bottom flask was charged with 20.4g of 2- trifluoromethylphenylacetic acid and 200 mL of anhydrous THF under a nitrogen atmosphere, and the mixture was cooled to -60 C in a dry ice/IPA bath. n-Hexyllithium (2.3 M in hexane; 43 mL) was added dropwise. maintaining the internal temperature below -50 0C The mixture was stirred at -60C for Ih. Additional n-hexyllithium (44 mL) was added dropwise, again maintaining the internal temperature below -50 C. The resulting yellow solution was stirred for Ih at -60 C, then 13 mL of l-bromo-3- chloropropane was added dropwise. After 3h, the mixture was allowed to stir with warming to room temperature overnight. The mixture was cooled to 0 C and treated with 300 mL of IN NaOH solution, maintaining the internal temperature below 15 C. The mixture was stirred for 10 min after addition and then the phases were split. The aqueous phase was cooled to 0 C and 6N HCl was added to adjust the pH to 2-3, again maintaining the internal temperature below 15 C. The solution was extracted with toluene (200 mL). The toluene phase was washed with water (2 x 80 mL). The organic phase was dried (T^SO,.), filtered, and concentrated by rotary evaporation to afford 26.9g of product (98 %).

Reference： [1]Patent: WO2010/25197,2010,A1 .Location in patent: Page/Page column 57; 58

40
[ 3038-48-0 ]
[ 140-88-5 ]
[ 1251864-78-4 ]

Reference： [1]Organic Syntheses,2016,vol. 92,p. 58 - 75
[2]Science,2010,vol. 327,p. 315 - 319

41
[ 1123196-11-1 ]
ethyl (E)-3-[6-methoxy-5-(4-methyl-1H-imidazol-1-yl)pyridin-2-yl]acrylimidate dihydrochloride [ No CAS ]
[ 3038-48-0 ]
[ 1123197-61-4 ]

Yield	Reaction Conditions	Operation in experiment
		Synthesis of (R) and (S)-2-{(E)-2-[6-methoxy-5-(4-methyl-1H-imidazol-1-yl)pyridin-2-yl]vinyl}-7-(2-trifluoromethylphenyl)-6,7-dihydro-5H-pyrrolo[1,2-b][1,2,4]triazole 55 mg of the racemic title compound was obtained from ethyl (E)-3-[6-methoxy-5-(4-methyl-1H-imidazol-1-yl)pyridin-2-yl]acrylimidate dihydrochloride (250 mg) and 4-chloro-2-(2-trifluoromethylphenyl)butyric acid hydrazide hydrochloride (212 mg) synthesised from (2-trifluoromethylphenyl)acetic acid by the same method as in Examples 253 and 254. The racemic title compound (55 mg) was separated by CHIRALPAK IB manufactured by Daicel Chemical Industries, Ltd. (2 cm * 25 cm; mobile phase: hexane:ethanol = 4:1) to obtain the title optically active compound with a retention time of 16 minutes (12 mg) and the title optically active compound with a retention time of 28 minutes (11 mg).

Reference： [1]Patent: EP2181992,2010,A1

42
[ 3038-48-0 ]
[ 1234562-68-5 ]

Reference： [1]Organic Letters,2010,vol. 12,p. 3140 - 3143
[2]Organic Letters,2020
[3]Organic Letters,2014,vol. 16,p. 6184 - 6187
[4]Organic Letters,2016,vol. 18,p. 5170 - 5173

43
[ 3038-48-0 ]
[ 99395-88-7 ]
[ 1240405-20-2 ]