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Product Details of 6-Methyl-4-Phenylchromanone

CAS No. :40546-94-9
Formula : C16H14O2
M.W : 238.28
SMILES Code : CC2=CC=C1OC(CC(C1=C2)C3=CC=CC=C3)=O
MDL No. :MFCD03695019
InChI Key :SUHIZPDCJOQZLN-UHFFFAOYSA-N
Pubchem ID :3791643

Safety of 6-Methyl-4-Phenylchromanone

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Application In Synthesis of 6-Methyl-4-Phenylchromanone

* 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.

  • Downstream synthetic route of [ 40546-94-9 ]

[ 40546-94-9 ] Synthesis Path-Downstream   1~2

  • 1
  • [ 40546-94-9 ]
  • [ 851789-43-0 ]
YieldReaction ConditionsOperation in experiment
97% A solution of 7-methyl-4-phenyl-3,4-dihydrocoumarin (compound of formula I) (9.52 g, 40.0 mmol) in dry tetrahydrofuran (50 ml) is added drop-wise to the cooled (0 °C) suspension of lithium aluminum hydride (3.04 g, 80 mmol) in 100 ml of dry tetrahydrofuran. The reaction mixture is stirred for 1 hour at room temperature under inert atmosphere and then the reaction is quenched by careful addition of 50 ml of a mixture tetrahydrofuran and water (1 :1) followed by acidification with 1 mol/l solution of hydrochloric acid (150 ml). The product is extracted with ethyl acetate. The combined organic phases are washed with water and brine, and dried over anhydrous magnesium sulphate. After removal of the solvents the compound of formula Il is obtained in 97 percent yield (9.68 g). It is recrystallized from diisopropylether yielding the product as white powder; mp = 112 - 115. 1H NMR (300MHz, DMSO-cfe): delta [ppm] = 2.08 - 2.17 (5H, m, CH3, CH2), 3.29 - 3.31 (2H, m, CH2), 4.38, 4.42 (2H, 2 x t, CH, OH), 6.63 (1 H, d, J = 8.0 Hz, 1 H-Ar), 6.76 (1 H, dd, J = 8.3, 1.7 Hz, 1 H-Ar), 7.00 (1 H, d, J = 1.7Hz, 1 H-Ar), 7.08 - 7.13 (2H, m, 1 H- Ph), 7.20 - 7.28 (3H, m, 4H-Ph), 9.04 (1 H, s, OH)13C NMR (300MHz, DMSO-Of6): delta [ppm] 20.5, 37.6, 39.1, 59.3, 115.0, 125.6, 127.0, 127.3, 127.9, 128.0, 130.9, 145.3, 152.4. ESI mass spectrum: 243 [M + H+]
86% EXAMPLE 1; Preparation of 3-(2-hydroxy-5-methylphenyl)-3-phenylpropanol (VIII) A basic aqueous solution of sodium borohydride prepared beforehand by dissolving 23.8 g (0.630 moles) of NaBH4 at ambient temperature in 170 ml of H2O and 3.5 ml of 30percent wt./vol. NaOH was added dropwise to a suspension of 3,4-dihydro-6-methyl-4-phenyl-2H-benzopyran-2-one of the formula (II) (100 g, 0.420 moles) in isopropanol (200 ml). Once addition was complete, the temperature was adjusted to 60° C. and the course of the reaction was monitored by TLC (eluent: cyclohexane/acetone: 70/30) until the substrate had completely disappeared. After 5 h, the reaction mixture was cooled to ambient temperature and HCl (2N) was added until a final pH of 7.0 was obtained. Stirring was continued for 30 min at ambient temperature, then the resultant suspension was filtered through a Buchner filter. The filtered solution was concentrated under reduced pressure and the crude residue was crystallised from toluene (280 ml) to yield 87.4 g (yield 86percent) of 3-(2-hydroxy-5-methylphenyl)-3-phenylpropanol (VIII) as a white solid.
70% Sodium borohydride (0.76 g, 20 mmol) is added in small portions to the cooled solution of 7-methyl-4-phenyl-3,4-dihydrocoumarin (compound of formula I) (0.48 g, 2 mmol) in 20 ml of methanol. The reaction mixture is stirred for 1 h at 0 °C and 4 h at room temperature. The reaction mixture is poured into 1 mol/l solution of hydrochloric acid (120 ml) and extracted with ethyl acetate (3 x 70 ml). The combined organic fractions are dried over anhydrous magnesium sulphate and the solvent evaporated to give the product in 70 percent yield (0.49 g).
Intermediate 6; 2-(3-hydroxy-1-phenyl-propy1 .-4-methyl-phenol; 6-methyl-4-phenyl-chroman-2-one, 250 gms was stirred in 1.25 liters methanol at room temperature. Sodium borohydride 70 gms was added slowly, whilst maintaining the temperature at room temperature. The reaction mixture was stirred for 18 hours. After completion of reaction, the pH of the reaction mass was adjusted to pH 5 using acetic acid. The reaction mixture was concentrated under vacuum and 2 liters of water were added. The reaction mass was stirred for 30 minutes and the solids filtered. The solids were dried at 55°C in a hot air oven for 20 hours. Weight 248 gms. Purification: Crude Intermediate I prepared as above was dissolved in 700 ml of toluene and heated to 85°C-87°C. The clear solution was gradually cooled to room temperature and stirred for 30 minutes. The solids were filtered and washed with toluene. The solids were dried in a hot air oven at 55°C-60°C. Yield: 222 gms. Mp (117-119°C)

  • 2
  • [ 40546-94-9 ]
  • [ 108-18-9 ]
  • [ 851789-43-0 ]
  • [ 124937-51-5 ]
  • [ 209747-04-6 ]
YieldReaction ConditionsOperation in experiment
Following procedure similar to that described in patent US-A-5 922 914, a solution of 100 mg (0.42 MMOL) of (IIA), having [a] D20 =-2. 8 (CHC13, c = 1.44) and prepared according to the preceding Example 2, in anhydrous toluene (3 ML), was placed in a 100-MT two-necked flask that had been flamed beforehand. A solution of 1 M. DIBAL in toluene (440 ul, 0.44 MMOL) was added dropwise to this solution, under N2 and AT-25GC. The reaction was monitored by GC-MS and was stopped with 3 ml of ethyl acetate AT-25°C after 5 h, when GC-MS showed there was formation of 6-methyl-4-phenyl-chroman-2-ol at 89percent, together with unreacted starting product (7percent) and a product of further reduction [3- phenyl-3 (2'hydroxy, 5 METHYL) PHENYL-PROPAN-1-OL] (4percent). 3 ml of a 23percent citric acid solution was added. The solution was stirred at room temperature over night. The organic phase was separated and washed with H20, dried over NA2SO4, filtered and the solvent was removed by evaporation at reduced pressure. The raw product thus obtained was placed in a glass cylinder in an autoclave. CH30H (5 ML), Pd/C 5percent (20 mg), (PRI) 2NH (147 LUI, 1.05 MMOL) and H2 were added at 5 atmospheres. The reaction was continued for 12 h at 48°C. The temperature was brought back to room temperature and the autoclave was depressurized by eliminating the gas. After filtration of the catalyst on celite, a GC-MS analysis was carried out, which showed 6-methyl-4-phenyl-chroman-2-ol (2percent), (IIA) 5percent, [3-PHENYL-3 (2 HYDROXY, 5 METHYL) PHENYL-PROPAN-1-OL] (16percent), and (S)- TOLTERODINE (77percent). The raw product was purified by flash chromatography on SI02 (hexane: EtOAc (7: 3) /Et3N 98: 2) to give a colourless oil (100 mg; 73percent); [a] D20 =-23 (c = 1.5 ; CH30H).
 

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