Structure of 50823-90-0
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CAS No. : | 50823-90-0 |
Formula : | C8H7F3O2 |
M.W : | 192.14 |
SMILES Code : | OCC1=CC=CC(OC(F)(F)F)=C1 |
MDL No. : | MFCD00061270 |
Boiling Point : | No data available |
InChI Key : | XRGSSROOYSFMMS-UHFFFAOYSA-N |
Pubchem ID : | 142783 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319 |
Precautionary Statements: | P264-P280-P302+P352+P332+P313+P362+P364-P305+P351+P338+P337+P313 |
* 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.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
11 mg (12%) | With trifluoroacetic acid; In tetrahydrofuran; 2-Chloro-4-(1-Piperazinyl)Pyrimidine.*; water; acetonitrile; tert-butyl alcohol; | Step 3: 4-(1-Piperazinyl)-2-[3-(Trifluoromethoxy)Benzyl]Oxy}Pyrimidine, Trifluoroacetate. A solution of 2-chloro-4-(1-piperazinyl)pyrimidine (0.04 g, 0.2 mmol; obtained in Step 2 above) and 3-trifluoromethoxybenzyl alcohol (0.077 g, 0.4 mmol) in tetrahydrofuran (4.0 ml) was treated with a solution of K-t-BuO in tert-butanol (1M; 0.4 mL, 0.4 mmol). The resulting mixture was heated at 70 C. overnight then allowed to cool. The solvent was evaporated under reduced pressure then the crude reaction mixture partitioned between ethyl acetate (4.0 mL) and water (2.0 mL). The organic phase was evaporated then purified by preparative C-18 HPLC using CH3CN/H2O/TFA (gradient: CH3CN 20% to 97%, TFA 0.1%) to afford 11 mg (12%) of the title compound. Purity 85% (HPLC). MS (ES+) m/z 355 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Example 15:; [2-(3-Acetyl-benzyl)-oxazol-4-yl]-carbamic acid 3-trifluoromethoxy-benzyl ester:; In a flame dried round-bottomed flask equipped with a magnetic stir bar and under inert atmosphere (N2), a solution of 2-(3-acetyl-benzyl)-oxazole-4-carbonyl azide (100 mg, 0.37 mmol) in xylene (2.0 mL) was heated to 140 0C for 5 min. <strong>[50823-90-0]3-(trifluoromethoxy)benzyl alcohol</strong> (711 mg, 3.70 mmol) was then added and the reaction mixture was further stirred at 140 0C for 5 min. The solvent was removed under reduced pressure. Purification of the residue by FC (9:1 ->; 3:7 hept-EA) followed by preparative HPLC gave the title compound as a white solid. LC-MS-conditions 02: tR = 1.09 min, [M+H]+ = 434.88. | ||
EXAMPLE 15[2-(3-Acetyl-benzyl)-oxazol-4-yl]-carbamic acid 3-trifluoromethoxy-benzyl esterIn a flame dried round-bottomed flask equipped with a magnetic stir bar and under inert atmosphere (N2), a solution of 2-(3-acetyl-benzyl)-oxazole-4-carbonyl azide (100 mg, 0.37 mmol) in xylene (2.0 mL) was heated to 140 C. for 5 min. <strong>[50823-90-0]3-(trifluoromethoxy)benzyl alcohol</strong> (711 mg, 3.70 mmol) was then added and the reaction mixture was further stirred at 140 C. for 5 min. The solvent was removed under reduced pressure. Purification of the residue by FC (9:1->3:7 hept-EA) followed by preparative HPLC gave the title compound as a white solid. LC-MS-conditions 02: tR=1.09 min, [M+H]+=434.88. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | With triphenylphosphine; diethylazodicarboxylate; In tetrahydrofuran; toluene; at 20℃; for 4h;Inert atmosphere; | (5A) Ethyl 3-ethoxy-3-(4-[3-(trifluoromethoxy)benzyl]oxy}phenyl)propionateEthyl 3-ethoxy-3-(4-hydroxyphenyl)propionate (100 mg, 0.420 mmol) produced in Example 1 (1C) and 3-trifluoromethoxybenzyl alcohol (123 mg, 0.640 mmol) were dissolved in tetrahydrofuran (2 mL), and triphenylphosphine (165 mg, 0.629 mmol) and a diethyl azodicarboxylate toluene solution (2.2 M, 290 μL, 0.638 mmol) were added thereto at room temperature, and then, the resulting mixture was stirred under a nitrogen atmosphere at room temperature for 4 hours. The solvent in the reaction solution was distilled off under reduced pressure, and the resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=100:0 to 95:5 (v/v)), whereby the objective title compound was obtained as a colorless oily substance (124 mg, 72%).1H NMR (CDCl3, 400 MHz): δ1.12 (3H, t, J=7.0 Hz), 1.21 (3H, t, J=7.0 Hz), 2.54 (1H, dd, J=5.1, 14.9 Hz), 2.78 (1H, dd, J=9.0, 14.9 Hz), 3.27-3.40 (2H, m), 4.11 (2H, q, J=7.0 Hz), 4.68 (1H, dd, J=5.1, 9.0 Hz), 5.05 (2H, s), 6.93 (1H, d, J=8.6 Hz), 7.16 (1H, m), 7.24-7.31 (3H, m), 7.34 (1H, m), 7.40 (1H, dd, J=7.8, 7.8 Hz) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
58% | 3-(Trifluoromethoxy)phenyl)methanol (0.31 g, 1.62 mmol) was dissolved in THF (8 mL) and sodium hydride (60% in oil, 0.071 g, 1.76 mmol) was added. The reaction was stirred for 20 min then 8-chloro-7-(4-chlorobenzyl)-1.3-dimethyl-1H-purine-2,6(3H,7H)-dione (0.50 g, 1.47 mmol, intermediate 35) was added. The reaction was stirred at room temperature for 15 h; then it was diluted with water (100 mL) and extracted with ethyl acetate (2*100 mL). The combined extracts were dried with magnesium sulfate, filtered and evaporated under reduced pressure to give an off-white solid. Solid was purified using a 40 g silica gel flash column eluted with 20% ethyl acetate/hexanes to give 7-(4-chlorobenzyl)-1,3-dimethyl-8-((3-(trifluoromethoxy)benzyl)oxy)-1H-purine-2,6(3H,7H)-dione (0.42 g, 58% yield) as a white solid. LCMS retention time=4.302 min and 99% purity, LCMS 495. 1H-NMR DMSO-d6 δ: 7.36-7.53 (m, 3H), 7.24-7.27 (m, 5H), 5.56 (s, 2H), 5.26 (s, 2H), 3.37 (s, 3H), 3.19 (s, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With tert.-butylhydroperoxide; copper(II) acetate monohydrate; calcium carbonate; In acetonitrile; at 80℃; for 24h; | General procedure: An oven-dried 15 mL glass vial with a magnetic stirrer bar was charged with Cu(OAc)2·H2O (12 mg, 6 mol%), N,O-dimethylhydroxylamine hydrochloride (2; 117 mg, 1.2 mmol), the respective benzyl alcohol 1 (1 mmol), aq 70% TBHP (0.17 mL, 1.2 mmol), CaCO3 (120 mg, 1.2 mmol) in MeCN (1 mL). The glass vial was flushed with N2 three times and the contents were stirred at r.t. for 1 h. Then the reaction mixture was stirred for 24 h at 80 C. After completion of the reaction, the mixture was cooled to r.t. All volatiles were removed under vacuum. The product was extracted with EtOAc (20 mL) and the organic layer was washed with sat. aq NaHCO3 (20 mL), dried (Na2SO4), and the solvent removed under vacuum. The Weinreb amide product 3 was purified by column chromatography (silica gel, 100-200 mesh) using a gradient of petroleum ether (bp 60-80 C) and EtOAc. All the amides were identified by GC-MS, 1H, and 13C NMR spectroscopic analysis. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With hydrogen; In methanol; at 20℃; for 5h; | General procedure: A mixture of 1a (196 mg, 1 mmol) and 1%Pd/Ni bimetallic catalyst9 (60 mg, 30 wt %) in MeOH (10 mL) was stirred underH2 at room temperature and atmospheric pressure (on an atmosphericpressure hydrogenation apparatus) until the absorption of hydrogen ceased(3.5 h). After the catalyst was removed off by a magnetic stirring bar, thesolution was evaporated in a vaporator to give the product 2a |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
8.2 mg | To (3- (trifluoromethoxy)phenyl)methanol (6.3 μ^, 8.1 mg, 0.042 mmol) dissolved in CH3CN (1 mL) was added NaH (2.8 mg, 0.116 mmol) and the resulting suspension was stirred for 10 min. at rt. Then 204 (10 mg, 0.0289 mmol) was added and the reaction mixture was stirred at rt for 2.5 h. MeOH (1 mL) was added and stirred for 5 minutes then the reaction mixture was concentrated under reduced pressure to give a residue which was partially purified by preparatory TLC (CH2Cl2:MeOH-NH3 (7 N), 20: 1) to afford 8.2 mg of intermediate nitrile (MS (m/z): [M+H]+ 516.2). A mixture of this and KOH (20.0 mg, 0.35 mmol) in t-BuOH (1 mL) was heated at 80 C for 1 h. Solvent was removed under reduced pressure and the residue was purified by preparatory TLC (CH2Cl2:MeOH-NH3 (7 N), 10: 1) to afford 6.6 mg (78%) of 205. 1H NMR (600 MHz, CDC13): δ 8.23 (s, 1H), 7.64 (d, J= 8.5 Hz, 2H), 7.25 (d, J= 7.9 Hz, 1H), 7.12 (d, J= 8.5 Hz, 2H), 7.09 (d, J= 8.7, 1H), 7.07 (t, J= 7.3, 1H), 7.05 (s, 1H), 6.00 (br s, 1H), 5.62 (br s, 1H), 5.37 (s, 2H), 3.93-3.99 (m, 1H), 3.78-3.87 (m, 1H), 3.45-3.56 (m, 1H), 3.03-3.40 (m, 1H), 2.77-2.86 (m, 1H), 2.34 (s, 6H), 2.20-2.25 (m, 1H), 1.90-1.96 (m, 1H); 13C NMR (150 MHz, CDC13 + CD3OD): δ 168.6, 168.2, 165.1, 160.2, 149.1, 143.7, 138.9, 129.9, 129.7, 127.8, 125.7, 125.6, 125.5, 121.9 (q, J= 255.6 Hz), 120.2, 119.9, 97.3, 66.7, 65.4, 51.1, 45.9, 44.3, 30.1; HRMS (ESI) m/z [M+H]+ calcd. for C25H27F3N503S, 534.1787; found 534.1782. |
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