1,3-diphenylpropan-1-one

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: β-Phenylpropiophenone (6-1) (7.5 g, 36.0 mmol) was suspended in ethanol (100 ml) and sodium borohydride (0.68 g, 18.0 mmol) was added under N2. The resulting solution was stirred at ambient temperature overnight. The ethanol was removed in vacuo and the residual oil-solid was taken up in ethyl acetate (100 ml) and water (30 ml). The ethyl acetate layer was removed, washed with water, dried, filtered and concentrated in vacuo to give 6-2 as a colorless oil. The ethanol was removed in vacuo The ethyl acetate layer was removed washed with water dried filtered concentrated in vacuo

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound was prepared as described in General Method 1 using 25 mmol of methyl acetoacetate, 27.5 mmol of NaH 60% dispersion in oil, 26.25 mmol of 1.6M n-butyl lithium in hexane, 25 mmol of 3-phenylpropiophenone and 70 mL of tetrahydrofuran. Upon concentrating the reaction a solid precipitated out which was triturated with ether and filtered (m.p. 130°-130.55,° C.). 1H NMR (CDCl3) δ 2.2-2.4 (m, 2 H), 2.4-2.6 (m, 1 H), 2.6-2.8 (m, 1 H), 2.9 (d, 1 H), 3.0 (d, 1 H), 3.3 (d, 1 H), 3.4 (d, 1 H), 7.0-7.5 (m, 15 H). Upon concentrating the reaction a solid precipitated out which was triturated with ether filtered (m.p. 130°-130.55,° C.)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (42) Chalcone (2.00 g, 9.60 mmol) dissolved in 24 ml of ethyl acetate was hydrogenated with 100 mg of 10% Pd/C at 55 psi for 2 hours at room temperature. The catalyst was filtered through celite, and the solvent evaporated to give the crude product, which was chromatographed on silica gel using 4:1 hexanes:ethyl acetate yielding 1.20 g (60.0%) of a white, flaky powder. 1H NMR (250 MHz) δ 8.00-7.97 (m, 2 H), 7.61-7.21 (m, 8 H), 3.36-3.30 (t, 2 H), 3.13-3.07 (t, 2 H); 13C NMR (62.7 MHz) 199.4, 141.5, 137.0, 133.3, 128.8, 128.6, 128.2, 126.3, 40.6 ppm. The catalyst was filtered through celite the solvent evaporated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: According to the general procedure, a solution of chalcone (50 mg, 0.24 mmol) and rac-32 (7.4 mg, 0.0047 mmol, 2.0 mol %) in CH2Cl2 (3 mL) was pressurized with H2 to 62 bar and stirred for 96 h. Filtration of the reaction mixture and evaporation of the solvent gave 41 as a colorless solid (50 mg, 99%). mp 69-70° C. (lit.2 70-72° C.); 1H NMR27 (300 MHz, CDCl3): δ 7.98 (d, 2H, J=7.2 Hz), 7.6-7.2 (m, 8H), 3.33 (t, 2H, J=7.8 Hz), 3.10 (t, 2H, J=7.2 Hz); 13C NMR (75.5 MHz, CDCl3): δ 199.3, 141.4, 136.9, 133.2, 128.7, 128.6, 128.5, 128.1, 126.2, 40.5, 30.2. Filtration of the reaction mixture and evaporation of the solvent

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (42) Chalcone (2.00 g, 9.60 mmol) dissolved in 24 ml of ethyl acetate was hydrogenated with 100 mg of 10% Pd/C at 55 psi for 2 hours at room temperature. The catalyst was filtered through celite, and the solvent evaporated to give the crude product, which was chromatographed on silica gel using 4:1 hexanes:ethyl acetate yielding 1.20 g (60.0%) of a white, flaky powder. 1H NMR (250 MHz) δ 8.00-7.97 (m, 2H), 7.61-7.21 (m, 8H), 3.36-3.30 (t, 2H), 3.13-3.07 (t, 2H); 13C NMR (62.7 MHz) 199.4, 141.5, 137.0, 133.3, 128.8, 128.6, 128.2, 126.3, 40.6 ppm. The catalyst was filtered through celite the solvent evaporated

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 1,3 diphenylpropan-1-one (231 mg, 1.1 mmol) in THF (2.5 mL) at −78° C. is added dropwise LiHMDS (1M in THF, 1.3 mL), over a period of 15 min. The mixture is stirred at −78° C. for 30 min then a solution of 2-benzyloxy-4-bromomethyl-1-nitrobenzene (321 mg, 1 mmol) in THF (2.5 mL) is added over a period of 15 min. The mixture is stirred at −78° C. for 15 min, then allowed to slowly warm to RT and stirred there for 45 min. The mixture is diluted with EtOAc, cooled to −25° C. and a solution of saturated ammonium chloride is added dropwise. The organic phase is washed with saturated ammonium chloride and brine, dried over MgSO4, filtered and concentrated to afford crude product which is purified using flash chromatography to give the title compound as a gum. The mixture is stirred at −78° C. for 15 min to slowly warm to RT stirred there for 45 min cooled to −25° C. The organic phase is washed with saturated ammonium chloride and brine dried over MgSO4 filtered concentrated to afford crude product which is purified

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 1,3-diphenylpropan-1-one (compound 2) (7.0 mmol) in 25 ml of anhydrous dioxane, a solution of bromine (7.0 mmol) in 10 ml of dioxane was slowly added dropwise over 30 min. The reaction mixture was left to stir at room temperature for 24 hrs to form 2-bromo-1,3-diphenylpropan-1-one (compound 3). Solvent was removed in vacuo. The 2-bromo-1,3-diphenylpropan-1-one product formed was determined by 1H NMR to be sufficiently pure to be used in the next step. The reaction mixture was left

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Chalcone (compound 1) (37.6 mmol) was dissolved in 250 ml of toluene (in some cases 25 ml of MeOH was added to insure a complete dissolution) and 400 mg of 10% Pd/C (0.01 eq) was added to the mixture. The compound was hydrogenated at 45 psi in a Parr apparatus for 40 min to 3 hrs to form 1,3-diphenylpropan-1-one (compound 2), during which time the reaction mixture was periodically checked for the starting material by TLC (Hex:EtOAc=1:1) to prevent over-reduction. Upon completion of reduction the reaction mixture was filtered through a short pad (2-3 inch) of silica gel and solvent was removed in vacuo to afford a crude product, which was either sufficiently pure to use in the next step or was purified by recrystallization from MeOH or Hex:EtOAc=3:1 or, in the case where over-reduction has occurred, by silica gel column chromatography using Hex:EtOAc=5:1 as an eluent. was added was added to the mixture The compound was hydrogenated at 45 psi in a Parr apparatus for 40 min to 3 hrs

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Chalcone (compound 1) (37.6 mmol) was dissolved in 250 ml of toluene (in some cases 25 ml of MeOH was added to insure a complete dissolution) and 400 mg of 10% Pd/C (0.01 eq) was added to the mixture. The compound was hydrogenated at 45 psi in a Parr apparatus for 40 min to 3 hrs to form 1,3-diphenylpropan-1-one (compound 2), during which time the reaction mixture was periodically checked for the starting material by TLC (Hex:EtOAc=1:1) to prevent over-reduction. Upon completion of reduction the reaction mixture was filtered through a short pad (2-3 inch) of silica gel and solvent was removed in vacuo to afford a crude product, which was either sufficiently pure to use in the next step or was purified by recrystallization from MeOH or Hex:EtOAc=3:1 or, in the case where over-reduction has occurred, by silica gel column chromatography using Hex:EtOAc=5:1 as an eluent. was added was added to the mixture The compound was hydrogenated at 45 psi in a Parr apparatus for 40 min to 3 hrs

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound was prepared as described in General Method 1 using 25 mmol of methyl acetoacetate, 27.5 mmol of NaH 60% dispersion in oil, 26.25 mmol of 1.6M n-butyl lithium in hexane, 25 mmol of 3-phenylpropiophenone and 70 mL of tetrahydrofuran. Upon concentrating the reaction a solid precipitated out which was triturated with ether and filtered (m.p. 130-130.55, °C.). 1H NMR (CDCl3) δ2.2-2.4 (m, 2H), 2.4-2.6 (m, 1H), 2.6-2.8 (m, 1H), 2.9 (d, 1H), 3.0 (d, 1H), 3.3 (d, 1H), 3.4 (d, 1H), 7.0-7.5 (m, 15H). Upon concentrating the reaction a solid precipitated out which was triturated with ether filtered (m.p. 130-130.55, °C.)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound was prepared as described in General Method 1 using 25 mmol of methyl acetoacetate, 27.5 mmol of NaH 60% dispersion in oil, 26.25 mmol of 1.6M n-butyl lithium in hexane, 25 mmol of 3-phenylpropiophenone and 70 mL of tetrahydrofuran. Upon concentrating the reaction a solid precipitated out which was triturated with ether and filtered (m.p. 130-130.55, °C.). 1H NMR (CDCl3) δ2.2-2.4 (m, 2H), 2.4-2.6 (m, 1H), 2.6-2.8 (m, 1H), 2.9 (d, 1H), 3.0 (d, 1H), 3.3 (d, 1H), 3.4 (d, 1H), 7.0-7.5 (m, 15H). Upon concentrating the reaction a solid precipitated out which was triturated with ether filtered (m.p. 130-130.55, °C.)