3-bromo-5-ethoxy-4-hydroxybenzaldehyde

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

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

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 suspension of sodium hydride (843 mg) in THF (5 mL) was added methanol (675 mg) under ice-cooling, and the mixture was stirred at room temperature for 0.5 hour. 3-Bromo-5-ethoxy-4-hydroxybenzaldehyde (1.29 g) in dimethylformamide (10 mL), and copper(I) chloride (31 mg) were added thereto, and the mixture was stirred at 120° C. for 4 hours under heating. The mixture was allowed to stand for cooling down to room temperature, diluted with ethyl acetate, washed with 1N hydrochloric acid, dried over anhydrous sodium sulfate, and then concentrated. The residue was purified by column chromatography on silica gel (hexane:ethyl acetate=2:1, v/v) to give the title compound (630 mg). cooling the mixture was stirred at 120° C. for 4 hours under heating for cooling down to room temperature washed with 1N hydrochloric acid dried over anhydrous sodium sulfate concentrated The residue was purified by column chromatography on silica gel (hexane

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

Procedure: A mixture of 3-bromo-5-ethoxy-4-hydroxybenzaldehyde (200 mg, 0.82 mmol) and copper (I) cyanide in DMF (5 mL) was refluxed overnight. The reaction mixture was diluted with water (20 mL), extracted with EtOAc, dried over Na2SO4, and concentrated under reduced pressure. Purified by column chromatography on silica gel to afford Intermediate 51 (70 mg, yield 45%). was refluxed overnight extracted with EtOAc dried over Na2SO4 concentrated under reduced pressure Purified by column chromatography on silica gel

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To the solution of 3-bromo-5-ethoxy-4-hydroxybenzaldehyde (1.00 g, 4.08 mmol) in pyridine (10 mL) was added Cu powder (0.52 g, 8.1 mmol) and methyl disulfide (0.77 g, 8.2 mmol), the mixture was then heated at 90° C. overnight. The reaction mixture was filtered, and the solvent was removed under reduced pressure, the residue was poured into water, and 6 N HCl (5 mL) was added, then the mixture was extracted with DCM (50 mL×3), the combined organic layers were washed with brine, dried over Na2SO4 and concentrated. The residue was purified by silica gel column (PE:EA=5:1) to give Intermediate 50 (600 mg, yield 69%). The reaction mixture was filtered the solvent was removed under reduced pressure the residue was poured into water, and 6 N HCl (5 mL) was added the mixture was extracted with DCM (50 mL×3) the combined organic layers were washed with brine dried over Na2SO4 concentrated The residue was purified by silica gel column (PE:EA=5:1)

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

Procedure: A solution of 3-bromo-5-ethoxy-4-hydroxybenzaldehyde (1.0 g, 4.1 mmol) in DMF (10 mL) was cooled at 0° C., NaH (180 mg, 4.5 mmol) was added, and the mixture was stirred for 15 minutes. MOM-Cl (360 mg, 4.5 mmol) was added, and the mixture was warmed to room temperature in two hours. TLC (PE:EtOAc=5:1) indicated that the starting material was consumed. Ice water was added to quench the reaction, and aqueous layer was extracted with EtOAc (30 mL×3). The combined organic layer was washed with brine (20 mL), dried over Na2SO4, filtered, concentrated, and purified by column chromatography to give 3-bromo-5-ethoxy-4-(methoxymethoxy)benzaldehyde (0.7 g, yield: 59.3%). was consumed Ice water was added to quench the reaction, and aqueous layer was extracted with EtOAc (30 mL×3) The combined organic layer was washed with brine (20 mL) dried over Na2SO4 filtered concentrated purified by column chromatography

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

Procedure: A solution of 3-bromo-5-ethoxy-4-hydroxybenzaldehyde (1.0 g, 4.1 mmol) in DMF (10 mL) was cooled at 0° C., NaH (180 mg, 4.5 mmol) was added, and the mixture was stirred for 15 minutes. MOM-Cl (360 mg, 4.5 mmol) was added, and the mixture was warmed to room temperature in two hours. TLC (PE:EtOAc=5:1) indicated that the starting material was consumed. Ice water was added to quench the reaction, and aqueous layer was extracted with EtOAc (30 mL×3). The combined organic layer was washed with brine (20 mL), dried over Na2SO4, filtered, concentrated, and purified by column chromatograph to give 3-bromo-5-ethoxy-4-(methoxymethoxy)benzaldehyde (0.7 g, yield: 59.3%). was consumed Ice water was added to quench the reaction, and aqueous layer was extracted with EtOAc (30 mL×3) The combined organic layer was washed with brine (20 mL) dried over Na2SO4 filtered concentrated purified by column chromatograph

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

Procedure: To a solution of 1,2-diphenylethanone (4.80 g, 25 mmol), 3-bromo-5-ethoxy-4-hydroxybenzaldehyde (5.00 g, 20 mmol) and urea (3.68 g, 61 mmol) in EtOH (250 mL) was added conc. HCl (10 mL). The mixture was heated at reflux for 112 h. Followed standard aqueous workup procedure and purified by silica gel column chromatography (PE:EA=1:3) to afford Compound 100 as a white solid (1.06 g, 11%). 1H NMR (MeOH-d4 500 MHz TMS): δ 7.24 (s, 5H), 7.09 (s, 1H), 7.04 (s, 3H), 6.85 (s, 3H), 5.17 (s, 1H), 4.03 (m, 2H), 1.37 (t, J=7.5 Hz, 3H); MS (ESI): m/z 465.0 [M+1]+. The mixture was heated at reflux for 112 h Followed standard aqueous workup procedure and purified by silica gel column chromatography (PE:EA=1:3)

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

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