Structure of 537039-44-4
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CAS No. : | 537039-44-4 |
Formula : | C8H8F3NO |
M.W : | 191.15 |
SMILES Code : | OCC1=CC(C(F)(F)F)=CC(N)=C1 |
* 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 |
---|---|---|
100% | To a suspension of lithium aluminum hydride (4 mmol, 152 mg) in THF (5 ml_) which is cooled to 0 0C is dropwise added a solution of <strong>[22235-25-2]3-amino-5-trifluoromethyl-benzoic acid methyl ester</strong> (2 mmol, 438 mg) in THF (1 mL) under nitrogen. The solution is allowed to warm to rt and stirred for 2 hours. To the solution is added diethyl ether (6 mL), then quenched with sodium sulfate decahydrate and brine. After decantation, the solution is dried over Na2SO4, filtrated, and concentrated under reduced pressure to give (3-amino-5- trifluoromethyl-phenyl)-methanol (quantitative yield), which is used in the next step without further purification); ESI-MS m/z: 192 [M+1]+, Retention time 1.30 min (condition A). | |
92% | With lithium aluminium tetrahydride; In tetrahydrofuran; at 20℃; for 1h;Cooling with ice; | (Reference Example 30) Synthesis of (3-amino-5-(trifluoromethyl)phenyl)methanol: To a solution of the compound of Reference Example 28 (0.4 g, 1.8 mmol) in tetrahydrofuran, lithium aluminium hydride (0.22 g, 5.7 mmol) was added portionwise under cooling on ice. The obtained reaction mixture was returned to room temperature and then stirred for one hour. After adding water to the reaction mixture to stop the reaction, the obtained solution was extracted with ethyl acetate and sequentially washed with a saturated aqueous solution of ammonium chloride and with saturated brine. The organic layer was dried over anhydrous sodium sulfate and then concentrated under vacuum, and the obtained crude product was purified by silica gel column chromatography (hexane:ethyl acetate = 1:1, Rf = 0.32) to obtain the title compound (0.32 g, 92%) (hereinafter referred to as the compound of Reference Example 30) as a white solid. MS(ESI) [M + H]+: 192. |
0.32 g | With lithium aluminium tetrahydride; In tetrahydrofuran;Cooling with ice; | To a solution of <strong>[22235-25-2]methyl 3-amino-5-(trifluoromethyl)benzoate</strong> (0.4 g, 1.825 mmol) in THF, lithium aluminium hydride (0.215 g, 5.66 mmol) was slowly added under cooling on ice. The ice bath was removed, and the obtained solution was stirred overnight. Water was slowly added to the reaction solution, and the obtained solution was extracted with ethyl acetate. The organic layer was sequentially washed with a saturated aqueous solution of ammonium chloride and with a saturated aqueous solution of sodium chloride. The obtained organic layer was dried over anhydrous sodium sulfate and then concentrated under vacuum, and the obtained crude product was purified by silica gel column chromatography (eluent; hexane:ethyl acetate = 90:10 ? 60:40) to obtain the title compound (0.32 g). MS(ESI) [M + H]+: 371. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69% | With tert.-butylnitrite; copper(ll) bromide; In acetonitrile; at 65℃; for 0.5h; | (3-Bromo-5-(trifluoromethyl)phenyl)methanol. (3-Amino-5-(trifluoromethyl)phenyl)methanol (1.6 g, 8.4 mmol) in dry acetonitrile (10 mL) was added dropwise to a solution of copper (II) bromide (2.24 g, 10.0 mmol) and tert-butyl nitrite (1.48 mL, 12.0 mmol) in acetonitrile (20 mL) at 65 C. After stirring for 30 min at 65 C., the reaction mixture was cooled to room temperature, poured into a 1 N hydrochloric acid solution, and extracted with ethyl acetate (2×). The organic layers were pooled together, washed with brine (2×), dried over sodium sulfate, and concentrated. Column chromatography on silica gel (20% ethyl acetate/hexanes) afforded 1.48 g (69%). 1H-NMR (CDCl3, 500 MHz) delta 7.71 (s, 1H), 7.68 (s, 1H), 7.55 (s, 1H), 4.75 (s, 2H). |
With tert.-butylnitrite; copper(ll) bromide; In acetonitrile; at 0 - 20℃; | (1) 3-Nitro-5-(trifluoromethyl)benzoic acid (5Og) is dissolved in tetrahydrofuran (300ml) and thereto is added dropwise a l.OM-borane tetrahydrofuran complex/ tetrahydrofuran (300ml) at 0C under nitrogen atmosphere over 2 hours and the mixture is stirred at 75C for 1 hour and a half. The reaction solution is allowed cool to room temperature and concentrated under reduced pressure, and thereto is added a IN- hydrochloric acid and the mixture is extracted with ethyl acetate. The organic layer is washed successively with water and a saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure to give crude (3-nitro-5-trifluoromethyl-phenyl)-methanol. The obtained crude product is dissolved in methanol (50OmL) and thereto is added 10% palladium-carbon (5g) and the mixture is stirred under hydrogen atmosphere at room temperature overnight. The catalyst is removed by filtration, and the filtrate is concentrated under reduced pressure to give crude (3-amino-5-trifluoromethyl-phenyl)-methanol. To copper (II) bromide (53.6g) is added acetonitrile (500ml), followed by an addition dropwise of tert-butyl nitrite (35.7ml) under ice-cooling and the mixture is stirred under nitrogen atmosphere for 5 minutes. To reaction mixture is added dropwise a solution of the above crude (3-amino-5-trifluoromethyl-phenyl)- methanol in acetonitrile (200ml) under ice-cooling over 1 hour and 15 minutes and the mixture is stirred at room temperature under nitrogen atmosphere overnight. To reaction mixture is added a lN-hydrochloric acid and the mixture is extracted with ethyl acetate. The organic layer is washed successively with a lN-hydrochloric acid, water and a saturated <n="166"/>brine, dried over magnesium sulfate, and concentrated under reduced pressure. The resulting residue is purified by silica gel column chromatography (hexane : ethyl acetate = 7:1?4:1) to give (3-bromo-5- trifluoromethyl-phenyl)-methanol (40.7g). NMR (CDCl3): 1.90 (lH,t), 4.76 (2H,d), 7.56 (IH, s), 7.68 (IH, s), 7.72 (lH,s) | |
With tert.-butylnitrite; copper(ll) bromide; In acetonitrile; at 0 - 20℃; | To copper (II) bromide (53.6 g) is added acetonitrile (500 ml), followed by an addition dropwise of tert-butyl nitrite (35.7 ml) under ice-cooling and the mixture is stirred under nitrogen atmosphere for 5 minutes. To reaction mixture is added dropwise a solution of the above crude (3-amino-5-trifluorornethyl- phenyl)-methanol in acetonitrile (200 ml) under ice-cooling over 1 hour and 15 minutes and the mixture is stirred at room temperature under nitrogen atmosphere overnight. To reaction mixture is added a lN-hydrochloric acid and the mixture is extracted with ethyl acetate. The organic layer is washed successively with a lN-hydrochloric acid, water and a saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The resulting residue is purified by silica gel column chromatography (hexane : ethyl acetate = 7: 1- >4: 1) to give (3-bromo-5-trifluoromethyl- phenyl)-methanol (40.7 g). NMR (CDCl3): 1.90 (lH,t), 4.76 (2H,d), 7.56 (IH, s), 7.68 (IH, s), 7.72 (lH,s). |
With tert.-butylnitrite; Bromoform; at 80℃; for 0.166667h; | [3-amino-5-(trifluoromethyl)phenyl]methanol (900 mg, 4.71 mmol) (Step A, Example 24) was suspended in CHBr3 (9 mL), and t-butyl nitrite (600 muL, 5.04 mmol) was added dropwise by syringe. The reaction was heated slowly to 80C and was maintained at this temperature for 10 minutes. The reaction was then cooled to room temperature, diluted with hexanes (50 mL), loaded on a silica gel column, and purified with 100% hexanes to 20% EtOAc/hexanes (2 columns) to afford [3-bromo-5- (trifluoromethyl) phenyl] methanol. Rf= 0.31 (25% EtOAc/hexanes). 'H NMR (CDC13, 500 MHz) No. 7.71 (s, 1H), 7.68 (s, 1H), 7.56 (s, 1H), 4.76 (d, J = 5.5 Hz, 2H), 1.86 (t, J = 5.7 Hz, 1H). Step B: 3-Bromo-5-(trifluoromethyl)benzaldehyde A solution of [3-bromo-5-(trifluoromethyl)phenyl]methanol (409 mg, 1.61 mmol) in CH2Cl2 (25 mL) was cooled to 0C and then Dess-Martin periodinane (1.02 g, 2.41 mmol) was added. The reaction was stirred at 0 C for 30 minutes and then warmed to room temperature. After stirring at room temperature for thirty minutes, the reaction was poured into IN NaOH (25 mL). The mixture was extracted with EtOAc (100 mL), and the organic extracts were washed with IN NaOH (25 mL), then brine (25 mL), dried over Na2S04, filtered, and concentrated. Purification by flash chromatography with 25% EtOAc/hexanes afforded 3-bromo-5- (trifluoromethyl)benzaldehyde. 0.60 (25% EtOAc/hexanes). 'H NMR (CDCI3, 500 MHz) 8 10.02 (s, 1H), 8.20 (s, 1H), 8.07 (s, 1H), 8.02 (s, 1H). |
Tags: 537039-44-4 synthesis path| 537039-44-4 SDS| 537039-44-4 COA| 537039-44-4 purity| 537039-44-4 application| 537039-44-4 NMR| 537039-44-4 COA| 537039-44-4 structure
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