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Quality Control of [ 91944-47-7 ]

COA NMR CNMR HPLC LC-MS

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Product Details of [ 91944-47-7 ]

CAS No. :	91944-47-7	MDL No. :	MFCD03092983
Formula :	C₃HF₃O₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	-
M.W :	126.03	Pubchem ID :	-
Synonyms :

Safety of [ 91944-47-7 ]

Signal Word:	Danger	Class:	3
Precautionary Statements:	P210-P240-P241-P242-P243-P261-P264-P270-P271-P280-P301+P312-P302+P352-P303+P361+P353-P304+P340-P305+P351+P338-P330-P332+P313-P337+P313-P362-P370+P378-P403+P233-P403+P235-P405-P501	UN#:	1989
Hazard Statements:	H224-H302-H315-H319-H335	Packing Group:	Ⅰ
GHS Pictogram:

Application In Synthesis of [ 91944-47-7 ]

* 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 [ 91944-47-7 ]
Downstream synthetic route of [ 91944-47-7 ]

[ 91944-47-7 ] Synthesis Path-Upstream 1~2

1
[ 50-00-0 ]
[ 91944-47-7 ]
[ 33468-69-8 ]

Yield	Reaction Conditions	Operation in experiment
13%	With ammonium hydroxide In methanol; water at 20℃; for 2 h;	Compound 216.1. 4-(Trifluoromethyl)-lH-imidazole. Into a 1000-mL round- bottom flask, was placed a solution of 3,3,3-trifluoro-2-oxopropanal (143 mL, 1 11.1 mmol) in a solvent mixture of methanol and water (200/200 mL). An aqueous solution of formaldehyde (350 mL, 116.67 mmol, 35percent) and ammonium hydroxide (30 mL, 25percent) were added to the reaction. The resulting solution was stirred for 2 h at room temperature, then concentrated under reduced pressure. The solids were collected by filtration to give 2 g (13percent) of the title compound as a white solid.

Reference： [1] Patent: WO2015/95767, 2015, A1, . Location in patent: Page/Page column 250

2
[ 75-07-0 ]
[ 91944-47-7 ]
[ 33468-67-6 ]

Yield	Reaction Conditions	Operation in experiment
54%	With ammonium hydroxide In methanol at 0 - 20℃; Sealed tube	Compound 16.2. 2-MethyI-4-(trifluoromethyl)-lH-imidazole. Into a 10-mL sealed tube, was placed a solution of acetaldehyde (296 iL, 5.29 mmol), 3,3,3-trifluoro-2- oxopropanal (compound 16.1, 1.0 g, 7.9 mmol), and 25percent ammonium hydroxide (0.8 mL) in methanol (5 mL). The solution was stirred for 3 h at 0 °C, then stirred at room temperature overnight. The resulting mixture was concentrated under reduced pressure and then the residue was diluted with water (50 mL) The aqueous phase was extracted with ethyl acetate (3 x 20 mL) and the combined organic extracts were dried (Na₂S0₄), filtered, and concentrated under reduced pressure. The crude product was purified by chromatography to yield 430 mg (54percent) of the title compound as a light yellow solid.
54%	With ammonium hydroxide In methanol at 0 - 20℃; Sealed tube	Compound 16.2. 2-Methyl-4-(trifluoromethyl)-lH-imidazole. Into a 10-mL sealed tube, was placed a solution of acetaldehyde (296 μ,, 5.29 mmol), 3,3,3-trifluoro-2- oxopropanal (compound 16.1, 1.0 g, 7.9 mmol), and 25percent ammonium hydroxide (0.8 mL) in methanol (5 mL). The solution was stirred for 3 h at 0 °C, then stirred at room temperature overnight. The resulting mixture was concentrated under reduced pressure and then the residue was diluted with water (50 mL) The aqueous phase was extracted with ethyl acetate (3 x 20 mL) and the combined organic extracts were dried ( a2S0₄), filtered, and concentrated under reduced pressure. The crude product was purified by chromatography to yield light yellow solid.

Reference： [1] Patent: WO2014/8197, 2014, A1, . Location in patent: Page/Page column 89
[2] Patent: WO2015/95767, 2015, A1, . Location in patent: Page/Page column 104

[ 91944-47-7 ] Synthesis Path-Downstream 1~6

1
[ 431-67-4 ]
[ 91944-47-7 ]

Yield	Reaction Conditions	Operation in experiment
31%	With sodium acetate; In water; at 100℃;	Compound 16.1. 3,3,3-T nfluoro-2-oxopropanal. Into a 100-mL round-bottom flask, was placed a mixture of 3,3 -dibromo- 1 , 1 , 1 -trifluoropropan-2-one (10.37 g, 38.43 mmol) and sodium acetate (12.61 g, 153.7 mmol) in water (50 mL). The resulting solution was stirred overnight at 100 C, then cooled to room temperature and extracted with ethyl acetate (3 x 20 mL). The combined organic extracts were dried (Na2S04), filtered, and concentrated under reduced pressure to yield 1.52 g (31 %) of the title compound as light yellow oil.
31%	With sodium acetate; In water; at 100℃;	Compound 16.1. 3,3,3-Trifluoro-2-oxopropanal. Into a 100-mL round-bottom flask, was placed a mixture of 3,3-dibromo-l, l, l-trifluoropropan-2-one (10.37 g, 38.43 mmol) and sodium acetate (12.61 g, 153.7 mmol) in water (50 mL). The resulting solution was stirred overnight at 100 C, then cooled to room temperature and extracted with ethyl acetate (3 x 20 mL). The combined organic extracts were dried ( a2S04), filtered, and concentrated under reduced pressure to yield 1.52 g (31%) of the title compound as light yellow oil.
24%	With water; sodium acetate; at 100℃;	INTERMEDIATE 43 3,3, 3-Trifluoro-2-oxoprop anal* 3, 3-Dibromo-l, l, l-trifluoroacetone (10.37 g, 38.43 mmol ; Intermediate 42) was dissolved in water (51.85 g). NaOAc (12.61 g, 153.72 mmol) was added and the resulting mixture was stirred at 100 C overnight. Extracted the mixture with EtOAc (50 mL) and evaporated the solvents from the organic phase. The residue was redissolved in EtOAc (20 mL) and filtration yielded 3,3, 3-trifluoro-2-oxopropanal (1.35 g, 24 %). *Previously described in Rec. Trav. Chim. Pays-Bas 1995,114, 97-102.

	With water; sodium acetate; at 100℃; for 12h;	A mixture of 3,3-dibromo-l,l,l-trifluoropropan-2-one 32 (38.4 mmol) and NaOAc (153.7 mmol) in H2O (50 mL) is heated at 100 0C for 12 h. Extraction of aqueous mixture with EtOAc (2 x 50 mL) and concentration of organic phase affords a crude oil. To the above residue is added DMF (30 mL), and the solution is cooled to 0 0C. Then a solution of Nl-benzylethane- 1,2-diamine (2.3 mL) in DMF (15 mL) is added. The resulting reaction mixture is stirred at rt for 12 h. Solvent is removed under vacuum to afford a residue which is dissolved in THF (15 mL) and citrate buffer (30 mL), followed by addition of IM NaBH3CN (25 mL). The mixture is stirred at rt for 12 h. The organic solvent is removed under vacuum and the resulting residue is basified to pH = 8 by addition of IN NaOH. Extraction of aqueous solution with DCM (2 x 50 mL) and concentration of the organic phase yield a crude oil which is purified by silica gel chromatography using a hexane : EtOAc = 3 : 1 to afford l-benzyl-3-(trifluoromethyl)piperazine 34a. 1H NMR (400MHz, J2-DCM) delta 7.37-7.25 (m, 5H), 3.57(d, 2H), 3.35-3.45 (m, IH), 3.05- 3.10 (m, IH), 2.87-3.00 (m, 2H), 2.74-2.80 (m, IH), 2.10-2.18 (m, 2H), 1.74 (s, IH). MS (m/z) (M+l)+: 245.1.
	With water; sodium acetate; at 100℃; for 0.5h;	Synthesis of 5-bromo-2-(2-chloro-6-fluorophenyl)-lH-imidazole-4-carbonitrile (1-10) [000218] 3,3-Dibromo-l,l,l-trifluoracetone (R-12) (37 mmol ) was added to a solution of NaOAc (70 mmol) in H2O (15 mL) and the mixture was heated for 30 minutes atlOO 0C. After cooling to room temperature, 2-chloro-6-fluoro benzaldehyde (R-13) (30 mmol) in MeOH (75mL) was added followed by cone. NH4OH (18 mL). The reaction mixture was allowed to stir for 12 hours and then the MeOH was removed under vacuum. The precipitate was collected by filtration, washed with water and dried under vacuum to yield 2-(2-chloro- 6-fluorophenyl)-4-(trifluoromethyl)-lH-imidazole (R-14). MS (m/z) (M+l)+: 265.1. [000219] A mixture of 2-(2-chloro-6-fluorophenyl)-4-(trifluoromethyl)- lH-imidazole (R-14) (1.4 mmol) and 5% NH4OH (200 mL) was heated to 60 0C. The reaction progress was monitored by TLC. The reaction was cooled to room temperature and carefully neutralized with glacial acetic acid to precipitate 2-(2-chloro-6-fluorophenyl)-lH-imidazole-4- carbonitrile (R-15). MS (m/z) (M+l)+: 300.2.[000220] To a solution of the 2-(2-chloro-6-fluorophenyl)-lH-imidazole-4-carbonitrile (R-15) (5.5 mmol) in DMF (50 mL) was added NBS (5.5 mmol). The resulting mixture was stirred for 2 hours at room temperature and then quenched with water (200 mL). The resulting precipitate was filtered and dried to yield 5-bromo-2-(2-chloro-6-fluorophenyl)-lH- imidazole-4-carbonitrile (1-10) as a white solid. 1H NMR (400MHz, J6-DMSO) delta 7.66 (m, IH), 7.55 (d, J = 8.0 Hz, IH), 7.47 (t, J = 8.0 Hz, IH). MS (m/z) (M+l)+: 299.0 and 301.4.
	With water; sodium acetate;	l,l-Dibromo-3,3,3-trifluroacetone was added to an aqueous sodium acetate solution. The mixture was heated until it was complete by GC. The reaction mixture, containing was then cooled and added to an ethanol/ethyl acetate solution of 4-(4-methylamino-3- nitrophenol)pyridine-2-carbaldehyde. After the addition was complete, ammonium hydroxide was added and the reaction mixture heated until the reaction was complete by HPLC. The reaction mixture was cooled and the product filtered and washed with water. The yellow solid (3) was then dried under vacuum until a constant weight is obtained.
	With sodium acetate; In water; for 0.5h;Reflux;	In stepl l-4, l,l,l-trifluoro-3,3-dibromoacetone (42 mg, 0.155 mmol) is added to a solution of sodium acetate trihydrate (42.3 mg, 0.31 mmol) in water. The mixture is stirred under reflux for 30 minutes in 115C oil bath to form 3,3,3-trifluoro-2-oxopropanal in-situ. After cooling to room temperature, the solution is added to a methanol (3 ml) solution containing (R)-4-((3- methyl-4-(5-(trifluoromethyl)pyridin-2-yl)piperazin-l-yl)methyl)-lH-pyrazole-3-carbaldehyde (50 mg, 0.141 mmol) and 0.5 ml of concentrated ammonium hydroxide. The mixture is stirred at room temperature for 16 hours and then concentrated and the residue is purified by HPLC (Cis column, eluted with CH3CN/H2O with 0.035% TFA). The factions containing product are combined, <n="80"/>Docket No.: P1325PC10neutralized with sodium carbonate, and extracted with ethyl acetate. The organic layers are then combined, dried, and concentrated to give (R)-2-methyl-4-((3-(4-(trifluoromethyl)-lH-imidazol-2- yl)-lH-pyrazol-4-yl)methyl)-l-(5-(trifluoromethyl)pyridin-2-yl)piperazine, 1H NMR (DMSOd6) delta 1.14 (d, 3H, J = 6.8 Hz), 2.06 (m, IH), 2.22 (m, IH), 2.86 (d, IH, J = 10.8 Hz), 2.99 (d, IH, J = 10.8 Hz), 3.09 (t, IH, J = 12 Hz), 3.72 (d, IH, J = 13.6 Hz), 3.80 (d, IH, J = 13.6 Hz), 4.16 (d, IH, J = 12.0 Hz), 4.58 (b, IH), 6.88 (d, IH, J = 8.8 Hz), 7.76 (s, IH), 7.78 (d, IH, J = 8.8 Hz), 7.79 (s, IH), 8.40 (s, IH); m/z [M++l] 460.2.

Reference： [1]Patent: WO2014/8197,2014,A1 .Location in patent: Page/Page column 89
[2]Patent: WO2015/95767,2015,A1 .Location in patent: Page/Page column 104
[3]Patent: WO2005/58858,2005,A1 .Location in patent: Page/Page column 120
[4]Archiv der Pharmazie,1989,vol. 322,p. 561 - 564
[5]Recueil des Travaux Chimiques des Pays-Bas,1995,vol. 114,p. 97 - 102
[6]Patent: WO2009/26276,2009,A1 .Location in patent: Page/Page column 59
[7]Patent: WO2010/127152,2010,A2 .Location in patent: Page/Page column 82-83
[8]Bioorganic and Medicinal Chemistry Letters,2015,vol. 25,p. 372 - 377
[9]Journal of Medicinal Chemistry,2017,vol. 60,p. 6942 - 6990
[10]Bioorganic and Medicinal Chemistry Letters,2018,vol. 28,p. 1887 - 1891
[11]Patent: WO2008/140850,2008,A1 .Location in patent: Page/Page column 60
[12]Patent: WO2009/123948,2009,A2 .Location in patent: Page/Page column 77; 78-79

2
[ 91944-47-7 ]
[ 4152-09-4 ]
1-benzyl-3-(trifluoromethyl)piperazine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
12%		INTERMEDIATE 44 l-Benzyl-3-(trifluoromethyl) piperazine* A solution of 3, 3,3-trifluoro-2-oxopropanal (0.31 g, 2.3 mmol; Intermediate 43) in DMF (10 mL) was cooled to 0 C and a solution of N-benzylethane-1, 2-diamine (0.37 g, 2.72 mmol) in DMF (10 mL) was added. After being stirred at room temperature overnight, the mixture was concentrated in vacuo. The residue was redissolved in THF (5 mL) and citrate buffer (5.3 mL ; 0.4 M), followed by NaBH3CN (0.31 g, 4.9 mmol), were added. The resulting mixture was stirred at room temperature overnight. The mixture was made basic (pH 8) with aqueous NaOH (8 mL; 1 M) and the aqueous layer was extracted twice with DCM (15 mL). The combined organic layers were dried (Na2SO4) and concentated. The residue was purified by LC-MS prep to give 1-benzyl-3- (trifluoromethyl) piperazine (66 mg, 12 %). HPLC 94 %, RT= 1.25 min (System A; 10-97 % MeCN over 3 min).'H NMR (270 MHz, CDC13) 8 ppm 2.77 (s, 2 H) 3.17-3. 31 (m, 1 H) 3.32-3. 64 (m, 3 H) 3. 83- 4.02 (m, 1 H) 4.13-4. 31 (m, 2 H) 6.68 (s, 1 H) 7.30-7. 55 (m, 5 H). MS (ESI+) m/z 245. *Previously described in Rec. Trav. Chim. Pays-Bas 1995,114, 97-102.
		A mixture of 3,3-dibromo-l,l,l-trifluoropropan-2-one 32 (38.4 mmol) and NaOAc (153.7 mmol) in H2O (50 mL) is heated at 100 0C for 12 h. Extraction of aqueous mixture with EtOAc (2 x 50 mL) and concentration of organic phase affords a crude oil. To the above residue is added DMF (30 mL), and the solution is cooled to 0 0C. Then a solution of Nl-benzylethane- 1,2-diamine (2.3 mL) in DMF (15 mL) is added. The resulting reaction mixture is stirred at rt for 12 h. Solvent is removed under vacuum to afford a residue which is dissolved in THF (15 mL) and citrate buffer (30 mL), followed by addition of IM NaBH3CN (25 mL). The mixture is stirred at rt for 12 h. The organic solvent is removed under vacuum and the resulting residue is basified to pH = 8 by addition of IN NaOH. Extraction of aqueous solution with DCM (2 x 50 mL) and concentration of the organic phase yield a crude oil which is purified by silica gel chromatography using a hexane : EtOAc = 3 : 1 to afford l-benzyl-3-(trifluoromethyl)piperazine 34a. 1H NMR (400MHz, J2-DCM) delta 7.37-7.25 (m, 5H), 3.57(d, 2H), 3.35-3.45 (m, IH), 3.05- 3.10 (m, IH), 2.87-3.00 (m, 2H), 2.74-2.80 (m, IH), 2.10-2.18 (m, 2H), 1.74 (s, IH). MS (m/z) (M+l)+: 245.1.

Reference： [1]Patent: WO2005/58858,2005,A1 .Location in patent: Page/Page column 120-121
[2]Recueil des Travaux Chimiques des Pays-Bas,1995,vol. 114,p. 97 - 102
[3]Patent: WO2009/26276,2009,A1 .Location in patent: Page/Page column 59

3
[ 60611-24-7 ]
[ 91944-47-7 ]
[ 1254171-18-0 ]

Yield	Reaction Conditions	Operation in experiment
	With ammonium hydroxide; In methanol; water; at 20℃; for 12h;	Synthesis of 4-bromo-2-(2-fluoro-6-(trifluoromethvl)phenvl)- lH-imidazole-5-carbonitrile (1-14)[000230] 3,3-Dibromo-l,l,l-trifluoracetone (R-12) (5.6 mmol ) was added to a solution of NaOAc (11.1 mmol) in H2O (3.0 mL) and the mixture was heated for 30 minutes atlOO C. After cooling to room temperature, <strong>[60611-24-7]2-fluoro-6-(trifluoromethyl)benzaldehyde</strong> (R-25) (4.45 mmol) in MeOH (20 mL) was added followed by cone. NH4OH (7 mL). The reaction mixture was allowed to stir for 12 hours and then the MeOH was removed under vacuum. The precipitate was collected by filtration, washed with water and dried under vacuum to yield 2-(2-fluoro-6-(trifluoromethyl)phenyl)-5-(trifluoromethyl)-lH-imidazole (R-26). MS (m/z) (M+ 1)+: 299[000231] A mixture of 2-(2-fluoro-6-(trifluoromethyl)phenyl)-5-(trifluoromethyl)- IH- imidazole (R-26) (3.4 mmol) and 5% NH4OH (60 mL) was heated to 60 0C. The reaction progress was monitored by TLC. The reaction was cooled to room temperature and carefully neutralized with glacial acetic acid to precipitate 2-(2-fluoro-6- (trifluoromethyl)phenyl)-lH-imidazole-5-carbonitrile (R-27). MS (m/z) (M+l)+: 256.0 [000232] To a solution of the 2-(2-fluoro-6-(trifluoromethyl)phenyl)-lH-imidazole-5- carbonitrile (R-27) (6.3 mmol) in DMF (50 mL) was added NBS (7.5 mmol). The resulting mixture was stirred for 2 hours at room temperature and then quenched with water (200 mL). The resulting precipitate was filtered and dried to yield 4-bromo-2-(2-fluoro-6- (trifluoromethyl)phenyl)-lH-imidazole-5-carbonitrile (1-14) 1H NMR (400MHz, J6-DMSO) delta 7.89 (m, 3H). MS (m/z) (M+l)+: 339.9

Reference： [1]Patent: WO2010/127152,2010,A2 .Location in patent: Page/Page column 86-87

4
[ 60611-22-5 ]
[ 91944-47-7 ]
[ 1254171-15-7 ]

Yield	Reaction Conditions	Operation in experiment
	With ammonium hydroxide; In methanol; water; at 20℃; for 12h;	Synthesis of 4-bromo-2-(2-chloro-6-(trifluoromethyl)phenyl)- lEta-imidazole-5-carbonitrile(1-13) [000227] 3,3-Dibromo-l,l,l-trifluoracetone (R-12) (12.0 mmol ) was added to a solution of NaOAc (24.0 mmol) in H2O (6.0 mL) and the mixture was heated for 30 minutes atlOO 0C. After cooling to room temperature, <strong>[60611-22-5]2-chloro-6-(trifluoromethyl)benzaldehyde</strong> (R- 22) (9.6 mmol) in MeOH (40 mL) was added followed by cone. NH4OH (14 mL). The reaction mixture was allowed to stir for 12 hours and then the MeOH was removed under vacuum. The precipitate was collected by filtration, washed with water and dried under vacuum to yield 2-(2-chloro-6-(trifluoromethyl)phenyl)-5-(trifluoromethyl)-lH-imidazole (R-23). MS (m/z) (M+ 1)+: 315.0[000228] A mixture of 2-(2-chloro-6-(trifluoromethyl)phenyl)-5-(trifluoromethyl)- IH- imidazole (R-23) (2.9 mmol) and 5% NH4OH (60 mL) was heated to 60 0C. The reaction progress was monitored by TLC. The reaction was cooled to room temperature and carefully neutralized with glacial acetic acid to precipitate 2-(2-chloro-6- (trifluoromethyl)phenyl)-lH-imidazole-5-carbonitrile (R-24). MS (m/z) (M+l)+: 272.0 [000229] To a solution of the 2-(2-chloro-6-(trifluoromethyl)phenyl)- lH-imidazole-5- carbonitrile (R-24) 1.8 mmol) in DMF (20 mL) was added NBS (1.95 mmol). The resulting mixture was stirred for 2 hours at room temperature and then quenched with water (10349.90 mL). The resulting precipitate was filtered and dried to yield 4-bromo-2-(2-chloro-6- (trifluoromethyl)phenyl)-lH-imidazole-5-carbonitrile (1-13) ) 1H NMR (400MHz, d6- DMSO) delta 8.17 (s, IH), 8.04(d, IH, J = 8.0 Hz), 7.97(m, IH). ). MS (m/z) (M+l)+:349.9

Reference： [1]Patent: WO2010/127152,2010,A2 .Location in patent: Page/Page column 85-86

5
[ 75-07-0 ]
[ 91944-47-7 ]
[ 33468-67-6 ]

Yield	Reaction Conditions	Operation in experiment
54%	With ammonium hydroxide; In methanol; at 0 - 20℃;Sealed tube;	Compound 16.2. 2-MethyI-4-(trifluoromethyl)-lH-imidazole. Into a 10-mL sealed tube, was placed a solution of acetaldehyde (296 iL, 5.29 mmol), 3,3,3-trifluoro-2- oxopropanal (compound 16.1, 1.0 g, 7.9 mmol), and 25% ammonium hydroxide (0.8 mL) in methanol (5 mL). The solution was stirred for 3 h at 0 C, then stirred at room temperature overnight. The resulting mixture was concentrated under reduced pressure and then the residue was diluted with water (50 mL) The aqueous phase was extracted with ethyl acetate (3 x 20 mL) and the combined organic extracts were dried (Na2S04), filtered, and concentrated under reduced pressure. The crude product was purified by chromatography to yield 430 mg (54%) of the title compound as a light yellow solid.
54%	With ammonium hydroxide; In methanol; at 0 - 20℃;Sealed tube;	Compound 16.2. 2-Methyl-4-(trifluoromethyl)-lH-imidazole. Into a 10-mL sealed tube, was placed a solution of acetaldehyde (296 mu,, 5.29 mmol), 3,3,3-trifluoro-2- oxopropanal (compound 16.1, 1.0 g, 7.9 mmol), and 25% ammonium hydroxide (0.8 mL) in methanol (5 mL). The solution was stirred for 3 h at 0 C, then stirred at room temperature overnight. The resulting mixture was concentrated under reduced pressure and then the residue was diluted with water (50 mL) The aqueous phase was extracted with ethyl acetate (3 x 20 mL) and the combined organic extracts were dried ( a2S04), filtered, and concentrated under reduced pressure. The crude product was purified by chromatography to yield light yellow solid.

Reference： [1]Patent: WO2014/8197,2014,A1 .Location in patent: Page/Page column 89
[2]Patent: WO2015/95767,2015,A1 .Location in patent: Page/Page column 104

6
[ 50-00-0 ]
[ 91944-47-7 ]
[ 33468-69-8 ]

Yield	Reaction Conditions	Operation in experiment
13%	With ammonium hydroxide; In methanol; water; at 20℃; for 2h;	Compound 216.1. 4-(Trifluoromethyl)-lH-imidazole. Into a 1000-mL round- bottom flask, was placed a solution of 3,3,3-trifluoro-2-oxopropanal (143 mL, 1 11.1 mmol) in a solvent mixture of methanol and water (200/200 mL). An aqueous solution of formaldehyde (350 mL, 116.67 mmol, 35%) and ammonium hydroxide (30 mL, 25%) were added to the reaction. The resulting solution was stirred for 2 h at room temperature, then concentrated under reduced pressure. The solids were collected by filtration to give 2 g (13%) of the title compound as a white solid.

Reference： [1]Patent: WO2015/95767,2015,A1 .Location in patent: Page/Page column 250

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P283	Wear fire/flame resistant/retardant clothing.
P284	Wear respiratory protection.
P285	In case of inadequate ventilation wear respiratory protection.
P231 + P232	Handle under inert gas. Protect from moisture.
P235 + P410	Keep cool. Protect from sunlight.
Response
Code	Phrase
P301	IF SWALLOWED:
P304	IF INHALED:
P305	IF IN EYES:
P306	IF ON CLOTHING:
P307	IF exposed:
P308	IF exposed or concerned:
P309	IF exposed or if you feel unwell:
P310	Immediately call a POISON CENTER or doctor/physician.
P311	Call a POISON CENTER or doctor/physician.
P312	Call a POISON CENTER or doctor/physician if you feel unwell.
P313	Get medical advice/attention.
P314	Get medical advice/attention if you feel unwell.
P315	Get immediate medical advice/attention.
P320
P302 + P352	IF ON SKIN: wash with plenty of soap and water.
P321
P322
P330	Rinse mouth.
P331	Do NOT induce vomiting.
P332	IF SKIN irritation occurs:
P333	If skin irritation or rash occurs:
P334	Immerse in cool water/wrap n wet bandages.
P335	Brush off loose particles from skin.
P336	Thaw frosted parts with lukewarm water. Do not rub affected area.
P337	If eye irritation persists:
P338	Remove contact lenses, if present and easy to do. Continue rinsing.
P340	Remove victim to fresh air and keep at rest in a position comfortable for breathing.
P341	If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P342	If experiencing respiratory symptoms:
P350	Gently wash with plenty of soap and water.
P351	Rinse cautiously with water for several minutes.
P352	Wash with plenty of soap and water.
P353	Rinse skin with water/shower.
P360	Rinse immediately contaminated clothing and skin with plenty of water before removing clothes.
P361	Remove/Take off immediately all contaminated clothing.
P362	Take off contaminated clothing and wash before reuse.
P363	Wash contaminated clothing before reuse.
P370	In case of fire:
P371	In case of major fire and large quantities:
P372	Explosion risk in case of fire.
P373	DO NOT fight fire when fire reaches explosives.
P374	Fight fire with normal precautions from a reasonable distance.
P376	Stop leak if safe to do so. Oxidising gases (section 2.4) 1
P377	Leaking gas fire: Do not extinguish, unless leak can be stopped safely.
P378
P380	Evacuate area.
P381	Eliminate all ignition sources if safe to do so.
P390	Absorb spillage to prevent material damage.
P391	Collect spillage. Hazardous to the aquatic environment
P301 + P310	IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
P301 + P312	IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.
P301 + P330 + P331	IF SWALLOWED: Rinse mouth. Do NOT induce vomiting.
P302 + P334	IF ON SKIN: Immerse in cool water/wrap in wet bandages.
P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
P303 + P361 + P353	IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.
P304 + P312	IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell.
P304 + P340	IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
P304 + P341	IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P305 + P351 + P338	IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P306 + P360	IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes.
P307 + P311	IF exposed: call a POISON CENTER or doctor/physician.
P308 + P313	IF exposed or concerned: Get medical advice/attention.
P309 + P311	IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician.
P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
P337 + P313	IF eye irritation persists: Get medical advice/attention.
P342 + P311	IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician.
P370 + P376	In case of fire: Stop leak if safe to Do so.
P370 + P378	In case of fire:
P370 + P380	In case of fire: Evacuate area.
P370 + P380 + P375	In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion.
P371 + P380 + P375	In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion.
Storage
Code	Phrase
P401
P402	Store in a dry place.
P403	Store in a well-ventilated place.
P404	Store in a closed container.
P405	Store locked up.
P406	Store in corrosive resistant/ container with a resistant inner liner.
P407	Maintain air gap between stacks/pallets.
P410	Protect from sunlight.
P411
P412	Do not expose to temperatures exceeding 50 oC/ 122 oF.
P413
P420	Store away from other materials.
P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
P410 + P403	Protect from sunlight. Store in a well-ventilated place.
P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling

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

[ CAS No. 91944-47-7 ] {[proInfo.proName]}

Quality Control of [ 91944-47-7 ]

Related Doc. of [ 91944-47-7 ]

Product Details of [ 91944-47-7 ]

Safety of [ 91944-47-7 ]

Application In Synthesis of [ 91944-47-7 ]

[ 91944-47-7 ] Synthesis Path-Upstream 1~2

[ 91944-47-7 ] Synthesis Path-Downstream 1~6

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry