1-(3-methoxyphenyl)propan-2-ol

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

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

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

Procedure: To a solution of 1-(3′-methoxyphenyl)-2-propyl alcohol 2 (0.98 g, 5.8 mmol) in 25 ml of HCl solution in 1,4-dioxane was added 4-nitrobenzaldehyde (0.91 g, 6.0 mmol) in one portion. The solution was refluxed for 4 hours. After removing the solvent under reduced pressure, the residue was washed with cold ethanol three times, affording the product 3 (1.62 g, yield 90%). 1HNMR(CDCl3): 8.20 (d, J=8.7 Hz, 2H), 7.50 (d, J=8,7 Hz, 2H), 6.65-6.48 (m, 3H), 5.78 (s, 1H), 4.01 (m, 1H), 3.76 (s, 3H), 2.80 (m, 2H), 1.40 (d, J=6.1 Hz). The solution was refluxed for 4 hours After removing the solvent under reduced pressure the residue was washed with cold ethanol three times

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

Procedure: To a solution of 3-methoxyphenylacetone (1, 1.0 g) in methanol (30 ml) was added NaBH4 (360 mg) in portions in the period of 20 min at 0° C. The resulting solution was stirred at such temperature for another 40 min. No more starting materials were detected from TLC. Ice water was added to the reaction slowly. It was extracted with CHCl3 three times. The combined organic phase was washed with brine, and dried over Na2SO4. Removal of the solvent afforded the crude product. Purification of the crude product by using a silica gel column gave the desired product 2 (1.01 g, 100%). It was extracted with CHCl3 three times The combined organic phase was washed with brine dried over Na2SO4 Removal of the solvent afforded the crude product Purification of the crude product

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

Procedure: Using the procedure described in Example 31 (Step 4), isomer (1) of 2-[4-(6-Methoxy-3-methyl-2-phenyl-naphthalen-1-yloxy)-benzylidene]-3-methyl-butyric acid ethyl ester (222-1) (0.159 g, 0.331 mmol), 1 N NaOH (4 mL), EtOH (3 mL) and THF (3 mL) afforded isomer (1) (223-1) 0.139 g (93%) of the title compound. 1H NMR (400 MHz, d-CDCl3): δ 1.22 (d, J=7.0 Hz, 6H), 2.23 (s, 3H), 3.08-3.15 (m, 1H), 3.93 (s, 3H), 6.58 (d, J=8.6 Hz, 2H), 7.04-7.07 (m, 3H), 7.12-7.13 (m, 3H), 7.20-7.28 (m, 4H), 7.54 (d, J=13.4, 2H), 7.76 (d, J=9.1 Hz, 1H).

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

Procedure: Treatment of 6-(methyloxy)-3-(3,3,3-trifluoropropyl)-3,4-dihydro-1(2H-naphthalenone (121) (0.40 g, 1.47 mmol) with bromine followed by DBU in CH3CN gave 0.47 g (92% from tetralone) of the title compound (122) as a white solid. 1H NMR (400 MHz, CDCl3): δ 2.40-2.55 (m, 2H), 3.05-3.10 (m, 2H), 3.91 (s, 3H), 6.06 (s, 1H), 7.02 (d, J=2.5 Hz, 1H), 7.12 (dd, J1=9.1 Hz, J2=2.5 Hz, 1H), 7.20 (s, 1H), 8.10 (d, J=9.1 Hz, 1H). LCMS (ESI): m/z 347 (M−H)−.

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

Procedure: To a cold solution (5° C.) of 1-[3-(methyloxy)phenyl]-2-propanol (1) (75 g, 0.45 mol) in CH2Cl2 (500 mL) were added Et3N (100 mL, 0.72 mol) and DMAP (2.75 g, 22.5 mmol). Methanesulfonic acid (52 mL, 0.675 mol) was added slowly (drop-wise) to the above reaction mixture at that temperature over a period of 40 min. The resultant mixture was stirred between 5° C. and 10° C. for 8 h under N2. The reaction mixture was washed with H2O (3×150 mL), brine (1×100 mL), dried (Na2SO4) and concentrated under reduced pressure to afford the crude product which was passed through a pad of silica to afford 108 g (98%) of the title compound. 1H NMR (400 MHz, CDCl3): δ 7.24 and 7.20 (dd, J1=15.2 Hz, J2=3.8 Hz, 1H), 6.81-6.76 (m, 3H), 4.87 (sextet, J=6.00 Hz, 1H), 3.77 (s, 3H), 2.96 and 2.92 (dd, J1=14.0 Hz, J2=8.0 Hz, 1H), 2.87 and 2.84 (dd, J1=14.0 Hz, J2=5.6, Hz, 1H), 2.54 (s, 3H), 1.44 (d, J=6.4 Hz, 3H). The reaction mixture was washed with H2O (3×150 mL), brine (1×100 mL) dried (Na2SO4) concentrated under reduced pressure to afford the crude product which

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

Procedure: To a cold solution (5° C.) of 1-[3-(methyloxy)phenyl]-2-propanone (75 g, 0.457 mol) in MeOH (500 mL) was added NaBH4 (19 g, 0.502 mol) portion-wise over a period of 0.5 h. The resultant mixture was stirred at that temperature for 1 h. Reaction mixture was quenched with 1 N aqueous HCl (250 mL) and concentrated under reduced pressure to remove most of the methanol. The reaction mixture was extracted with EtOAc (3×150 mL). The combined organic layer was washed with water (1×100 mL), brine (1×100 mL), dried (Na2SO4) and concentrated under reduced pressure to afford the crude product. The reaction mixture was just passed through a pad of silica gel and washed with 1:1 hexanes:EtOAc to afford 75 g (99%) of the title compound. 1H NMR (400 MHz, CDCl3): δ 7.24-7.20 (m, 1H), 6.80-6.75 (m, 3H), 4.02-3.97 (m, 1H), 3.79 (s, 3H), 2.78-2.63 (m, 2H), 1.25-1.19 (m, 3H). Reaction mixture was quenched with 1 N aqueous HCl (250 mL) concentrated under reduced pressure to remove most of the methanol The reaction mixture was extracted with EtOAc (3×150 mL) The combined organic layer was washed with water (1×100 mL), brine (1×100 mL) dried (Na2SO4) concentrated under reduced pressure to afford the crude product washed with 1:1 hexanes