| 97% |
With 3-chloro-benzenecarboperoxoic acid In dichloromethane at 20℃; for 24h; Inert atmosphere; |
10.2 4.10.2. 4-Methoxycarbonylpyridine N-Oxide
Methyl isonicotinate (1.8 mL, 15.2 mmoles) and m-chloroperoxybenzoicacid (6.8 g, 30.4 mmoles) were dissolved in dry dichloromethane(150 mL) in a flame-dried flask. This reaction mixture wasstirred at room temperature for 24 h. The solution was concentratedunder reduced pressure, and the resulting residue was purifiedby chromatography on silica (1-4% v/v MeOH in acetone) toafford the title compound as a white solid (2.26 g, 97%) with mp118.1-121.3 C. 1H NMR (400 MHz, CDCl3, d): 8.20 (d, J = 4.0 Hz, 2H), 7.84 (d, J = 4.0 Hz, 2H), 3.90 (s, 3H); 13C NMR (100 MHz, CDCl3,d): 163.7, 139.4, 126.5, 126.4, 52.8; HRMS (ESI) m/z 154.0492[calc’d for C7H8NO3 (M+H)+ 154.0499]. |
| 95% |
With dihydrogen peroxide; methyltrioxorhenium(VII) In dichloromethane; lithium hydroxide monohydrate at 20℃; Inert atmosphere; |
|
| 95.2% |
With dihydrogen peroxide; glacial acetic acid at 70℃; |
isonicotinic acid methyl ester (20g, 145.8mmol) in the reaction bottle, acetic acid is added 120 ml, stirring, added to the reaction bottle 30% hydrogen peroxide (16.5g, 145 . 6mmol), 70 °C heating and stirring, 3h after, adding 30% hydrogen peroxide (11.6g, 102 . 3mmol), heating is continued stirring, after TLC monitoring reaction end, concentrated, water 50 ml, dichloromethane is used for 500 ml extraction, drying of the organic phase is concentrated, add hexane agitation washing, filtering, to obtain light yellow crystalline solid, 50 °C vacuum drying, be 21.26g, yield: 95.2% |
| 95.2% |
With dihydrogen peroxide In glacial acetic acid at 70℃; |
1.1 Example 1 Preparation a isonicotinate N- oxide implementation:
The isonicotinate (20g, 145.8mmol) placed in a reaction flask, acetic acid 120ml, stirring, to the reaction flaskWithin 30% hydrogen peroxide (16.5g, 145.6mmol), 70 heating and stirring, 3h later, additional 30% hydrogen peroxide (11.6g,102.3mmol), continued heating and stirring, TLC monitoring After the reaction was concentrated, water was added 50ml, extracted with dichloromethane 500ml,The organic phase was dried and concentrated, hexane added to stir washing, suction filtration to give a pale yellow crystalline solid, 50 deg.] C and dried in vacuo to afford 21.26g,Yield: 95.2% |
| 93% |
With dihydrogen peroxide; methyltrioxorhenium(VII) In dichloromethane at 24℃; for 12h; Inert atmosphere; |
|
| 92% |
With dihydrogen peroxide; glacial acetic acid at 70℃; |
|
| 91% |
Stage #1: 4-pyridinecarboxylic acid, methyl ester With 3-chloro-benzenecarboperoxoic acid In dichloromethane for 6h; Inert atmosphere; Reflux;
Stage #2: With potassium carbonate In dichloromethane Inert atmosphere; |
|
| 87% |
With dihydrogen peroxide In methanol at 60℃; for 0.05h; Flow reactor; Schlenk technique; Green chemistry; |
N-Oxidation of 3-Methylpyridine; Typical Procedures
General procedure: Continuous flow process: TS-1 catalyst (955 mg) was prepared to 40- 60 mesh of particle, which was filled in a packed-bed microreactor. A liquid phase plunger pump was then connected to the column, and the parameters were set with a 0.6 mL/min flow rate. The reaction mixture of 3-methylpyridine (1a; 0.25 mol/L) and H2O2 (0.275 mol/L) with CH3OH as the solvent was prepared, which connected with the plunger pump. Then the micro stainless steel column was put into a 60 °C water bath, and the pump was started. After a few minutes, 2.0 mL of the reaction mixture was collected. Next, CH3OH in the solution was removed by vacuum rotary evaporation, and the residue was purified by flash column chromatography (silica gel) to give the desired product 2a and unreacted 1a. Another 2.0 mL of the reaction mixture was measured for the calculation method for XH2O2 and UH2O2 by KMnO4 titration method. |
| 78% |
With 3-chloro-benzenecarboperoxoic acid In dichloromethane |
11.1 Step 1 . 4-(Methoxycarbonyl)pyridine 1 -oxide.
A solution of methyl pyridine- 4-carboxylate (3 g, 21 .88 mmol, 1 .00 equiv) and m-chloroperbenzoic acid (5 g, 28.97 mmol, 1 .32 equiv) in DCM (30 mL) was stirred overnight at ty. The precipitated product was collected by filtration to give 2.6 g (78%) of 4- (methoxycarbonyl)pyridine 1 -oxide as an off-white solid. LC/MS (Method J, ESI): RT= 0.89 min, m/z = 1 4.0 [M+H]+ . |
| 70% |
With dihydrogen peroxide; glacial acetic acid |
|
| 65% |
With dihydrogen peroxide In lithium hydroxide monohydrate; glacial acetic acid |
31.1 Step 1
Step 1 Preparation of Methyl Isonicotinate N-Oxide: To a solution of hydrogen peroxide (43 mL) in 250 mL of acetic acid was added methyl isonicotinate. The reaction mixture was stirred at 80° C. overnight (about eighteen hours). The solution was concentrated to about 50 mL, water was added and the mixture was saturated with sodium carbonate. The aqueous phase was extracted with methylene chloride. The organic layer was washed with brine, dried over magnesium sulfate and filtered. The filtrate was concentrated and trituated with hexane. The resulting precipitate was filtered and air-dried to give 24.5 g (65% yield) of product as a white solid: mp: 118-120° C. |
| 46% |
With 3-chloro-benzenecarboperoxoic acid In dichloromethane at 20℃; for 3h; Sealed tube; |
|
|
With Perbenzoic acid In 1,4-dioxane; lithium hydroxide monohydrate at 20℃; other temp. (25, 30 deg C); ΔS(excit.); |
|
|
With dihydrogen peroxide; glacial acetic acid |
|
|
Stage #1: 4-pyridinecarboxylic acid, methyl ester With dihydrogen peroxide In dichloromethane at 20℃;
Stage #2: In dichloromethane at 20℃; for 1h; |
51
According to Scheme 52, to a solution of compound 82 (13.7 g, 0.1 mol) in CH2C12 at room temperature was added H202 (20 mL, 50% v/v, Aldrich), and methyltrioxorhennium (MTO, 250 mg, 1 mmol, Aldrich). The resulting mixture was stirred at room temperature for 12 h. Mn02 (25 mg) was added and the mixture was left at room temperature for 1 h or until there is no more gas release (02) from the mixture. The organic layer of the mixture was separated, and the aqueous layer was extracted with CH2C12 (100 mL). The combined organic layers were dried over Na2S04, filtered, and concentrated to dryness. The residue was washed with 30% EtOAc/Hexane and the solid was dried under vacuum to give compound 83 (12.7 g, 84 mmol). |
|
With 3-chloro-benzenecarboperoxoic acid In acetonitrile at 95℃; Flow reactor; |
Flow synthesis of methyl 2-cyanoisonicotinate (4)
A solution of methyl 4-carboxypyridine (1M in MeCN) and a solution of mCPBA (1M in MeCN) were flowed via a T-mixer into a 10mL flow reactor at 95°C at a rate of 1.0mL per minute (Scheme 3). The solution of methyl 4-carboxypyridine N-oxide exiting the first reactor was combined with TMSCN/NEt3 (1:2.5, 1M in MeCN) via a second T-mixer. This solution was flowed into a 5mL reactor at 150°C at a rate of 0.2mL per minute. The solution exiting the reactor was collected and the solvent evaporated to provide methyl 2-cyanoisonicotinate (4). |
|
With 3-chloro-benzenecarboperoxoic acid In dichloromethane at 20℃; for 18h; |
|
|
Stage #1: 4-pyridinecarboxylic acid, methyl ester With 3-chloro-benzenecarboperoxoic acid In dichloromethane at 0 - 20℃; for 6h;
Stage #2: With triphenylphosphine In dichloromethane at 20℃; for 4h; |
|
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
For Research Only
120K+ Compounds
Competitive Price
1-2 Day Shipping
