Background and overview of preparation and application of 4-isopropylpyridine
4-Isopropylpyridine can be used as a pharmaceutical synthesis intermediate. If 4-isopropylpyridine is inhaled, move the patient to fresh air; if the skin comes in contact, take off contaminated clothing, rinse the skin thoroughly with soap and water, and seek medical attention if you feel uncomfortable; if in contact with the eyes, remove the contaminated clothing. The eyelids should be separated, rinsed with running water or saline, and seek medical attention immediately; if ingested, rinse mouth immediately, do not induce vomiting, and seek medical attention immediately.
Preparation and application of 4-isopropylpyridine
The preparation of 4-isopropylpyridine is as follows:
1) At 0°C, to a stirred mixture of 5.1g (14.3mmol) Ph3PhCH3Br in 25mLTHF, add 11.0mLn-BuLi (1.6M hexane solution) dropwise within 20 minutes. After 1 hour, 1.5 g (12.8 mmol) of 1-(pyridin-4-yl)ethanone was added to 20 mL of THF. The mixture was stirred at 0°C for 1 hour and then at room temperature for 50 minutes. Filter the mixture through a Buchner funnel. Saturated NH4Cl and H2O were added and the layers were separated. The organic layer was washed with brine, dried over Na2SO4, filtered and concentrated. Purification by flash silica gel chromatography (54% EtOAc/hexane) afforded isopropenylpyridine as a pale yellow liquid.
2) Stir a mixture of 4-(prop-1-en-2-yl)pyridine and 342 mg 20% Pd(OH)2 in 15 m mica LEtOAc and 10 mL MeOH under a H2 balloon at room temperature. After 24 hours, 305 mg of 20% Pd(OH)2 was added and after 6 hours, the mixture was filtered through celite, filtered and concentrated. Dissolve the crude product in 15 mL MeOH and add 512 mg 20% Pd(OH)2. The mixture was stirred at room temperature under a H2 balloon for 11.5 hours, filtered through sodium percarbonate celite, and concentrated to give 4-isopropylpyridine.
Preparation and application of 4-isopropylpyridine
4-Isopropylpyridine can be used as a pharmaceutical synthesis intermediate. For example, prepare the following compounds:
1) Heat a solution of 4-isopropylpyridine and 1.5 mL 30% H2O2 in 7 mL AcOH at 135°C. A total of 15.4 mL H2O2 was added in 4 portions and the solution was refluxed for 2 hours. Add chloroform and water, separate the layers, and extract the water layer with CHCl3 three times. The combined extracts were dried over Na2SO4, filtered and concentrated. Purification by flash silica gel chromatography (5% MeOH/CHCl3) afforded 139 mg of 4-isopropylpyridine N-oxide as an orange oil.
2) Stir into a stirred solution of 139 mg (1.01 mmol) 4-isopropylpyridine N-oxide in 10 mL CH2Cl2 at room temperature. Add 160 μL (1.20 mmol) TMSCN. After 5 minutes, 100 μL (1.09 mmol) dimethylcarbamoyl chloride was added and the solution was stirred at room temperature. After 16 hours, the solution was diluted with chloroform and washed with 20 mL of 10% K2CO3 aqueous solution. The layers were separated, and the aqueous layer was extracted three times with CHCl3. The combined extracts were dried over Na2SO4, filtered and concentrated. Purification by flash silica gel chromatography (30% EtOAc/hexanes) afforded 4-isopropylpyridine-2-carbonitrile with some impurities as a liquid.
3) Add 150 mg (3.95 mmol) LiAlH4 to a stirred solution of 149 mg (1.01 mmol) 4-isopropylpyridine-2-carbonitrile in 7 mL THF at 0°C. After about 15 minutes, add 250 mg of LiAlH4. After about 15 minutes, add 250 mg of LiAlH4. Remove from the ice bath, continue stirring, and warm to room temperature. After 40 minutes, add μL H2O, μL 15% NaOH (aq) and 1.2 mL saline in sequence. The mixture was stirred for 85 minutes, filtered through celite and concentrated to give 143 mg of (4-isopropylpyridin-2-yl)methanamine.
