3′-Methoxypropiophenone

To a stirredsolution of 14 (5.86 g, 30.0 mmol) in THF (150 mL) was slowly added EtMgBr (0.960 mol/L in THF, 100 mL, 96.0 mmol)at 0To a stirred solution of /V-methyl-/V, 3-bis(methyloxy)benzamide 1 (9.0 g, 0.046 mol) in THF was added 3.0 M solution of ethyl magnesium bromide (23 mL, 0.069 mol) slowly at 5To a stirred solution of Λ/-methyl-Λ/, 3-bis(methyloxy)benzamide V\_ (9.0 g, 0.046 mol) in THF was added 3.0 M solution of ethyl magnesium bromide (23 ml_, 0.069 mol) slowly at 5Ethyl magnesium bromide in diethyl ether (48.6 mL, 48.6 mmol) was added dropwise at 0Example 1Preparation of 3-Methoxy propiophenone[0071] 3 -Hydroxy propiophenone (250 g) and potassium hydroxide (94 g) were taken into a round bottom flask, acetone (1000 ml) was added to the resulting mixture and then stirred for 30 minutes at 40°C. Potassium carbonate (60 gm) and tetrabutylammonium bromide (20 gm) were added to the reaction mass, followed by the addition of methyl iodide (260 g) at 40- 45°C and then stirring for 12 hours at the same temperature. After completion of the reaction, the reaction mass was filtered, washed with acetone (50 ml) and the solvent was distilled under vacuum at temperature 40°C. Water (500 ml) and dichloromethane (600 ml) were added to the concentrated reaction mass, the resulting mass was stirred for 30 minutes and then the layers were separated. The aqueous layer was extracted with dichloromethane (400 ml). The organic layers were combined, washed with water (2 x 250 ml) and then dried over anhydrous sodium sulphate. The residue was exposed to vacuum at 40°C till constant weight. The resulting crude product was purified under high vacuum distillation (conditions for HVD: External temperature: 130-140°C; Vapor Temperature: 90-92°C at 5mm/Hg vacuum) to give 206 g of 3-methoxy propiophenone (Yield: 99percent).The amount of methoxyphenylbromobenzene was increased to 243.2 g (1.3 mol), propionitrile 71.6 g (1.3 mol), the same as Example 1, The yield of methoxyphenylacetone was 88.6percent.;_In the presence of reflux condenser, The reaction flask of the dropping funnel was charged with 24.0 g (1.0 mol) of magnesium powder, Anhydrous aluminum trichloride 3.0 g, Tetrahydrofuran (THF) solution (300 mL)heating.In the dropping funnel, 187.1 g (1.0 mol) of m-methoxybenzene was slowly added, And 300 mL of tetrahydrofuran (THF)Control reaction liquid temperature 50-55 , So that the solution has been kept in a state of slightly boiling, After the dropwise addition was heated under reflux 0.5-1.0h, To ensure that the magnesium reaction is complete, Get Grignard reagent.Stirring, 55.1 g (1.0 mol) of propionitrile was slowly added to the Grignard reagent, After the dropwise addition, And then reaction 1.0-2.0h.Reaction is completed, Cold water bath slowly drop by adding 3.0mol / L hydrochloric acid, Decomposition of addition products, The inorganic phase is separated, The organic phase was subjected to atmospheric distillation to remove THF.Control the temperature to 180-185 ° C, The distillation was carried out under reduced pressure (reduced pressure at -0.095 MPa, Distillation temperature of 185 ° C), 3-Methoxyphenylacetone was obtained in a yield of 78.3percent.General procedure: In a sealed tube, under nitrogen atmosphere, the ruthenium complex [RuCl2( 6-C6H6)(PTA-Me)] (3a) (0.02–0.1 mmol; 0.5–2.5 molpercent of Ru) and K2CO3 (0.05–0.25 mmol; 1.25–6.25 molpercent) were added to a solution of the corresponding allylic alcohol 4a–o (4 mmol) in tetrahydrofuran (4 mL), and the resulting mixture stirred at 75 °C for the indicated time (see Table 4 and Scheme 3). The course of the reaction was monitored by taking regularly samples of ca. 10 L which after dilution with dichloromethane (3 mL) were analyzed by GC. After the reaction was finished, the mixture was cooled to room temperature leading to the partial precipitation of 3a. The solid was separated by filtration and the reaction product isolated by solvent removal and chromatographic workup of the residue on silica-gel using a mixture of EtOAc–hexane (1:10) as eluent. The identity of the resulting carbonyl compounds 5a–o was assessed by comparison of their retention times with those of commercially available pure samples (Sigma–Aldrich or Acros Organics), by their fragmentation in GC/MS, and/or NMR spectroscopy.To a mixture of 1.95 g of N, 3-dimethoxy-N-meth- ylbenzamide mentioned in Reference Production Example 23 and 20 mE of tetrahydrofuran, 15.8 mE of ethylmagnesium bromide (13percent tetrahydrofuran solvent) was added at 0° C., followed by stirring at room temperature for 2 hours. To the reaction solution, water was added and the mixture was extracted with ethyl acetate. The organic layer was washed with water and a saturated saline solution, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure to obtain 1.73 g of 1 -(3-methoxyphenyl)propan-1-one. EXAMPLE 27 Example 30 The intermediate 1- (3-methoxyphenyl) propan-1-one (200 mg, 1.22 mmol) and 1H-indole-3-carbaldehyde (58.94 mg, 0.41 mmol) were dissolved in a solution of ethanol (5 mL)Add piperidine (0.3mL) and stir at 95 C for 48h.The organic phase was spin-dried, and the remaining crude product was recrystallized from ethanol to obtain the target compound.(E) -1- (E) -3- (1H-indol-3-yl) -1- (3-methoxyphenyl) -2-methylprop-2-en-1-one54.4 mg, yield 46%.

Molecular Weight:164.20
XLogP3:2.3
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:3
Exact Mass:164.083729621
Monoisotopic Mass:164.083729621
Topological Polar Surface Area:26.3
Heavy Atom Count:12
Complexity:154
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes