3-methoxy-4-(2-methoxyethoxy)benzaldehyde

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

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

Procedure: To a N2-purged flask was added 3-methoxy-4-(2-methoxy-ethoxy)-benzaldehyde from Step A (162 mg, 771 mmol), rhodanine (103 mg, 1 equiv), NaOAc (190 mg, 2.31 mmol) and HOAc (3 mL). The mixture was stirred and heated at 90° C. for 14 h under a condenser, resulting in a yellow precipitate. The reaction mixture was diluted with water (100 mL) and the solid precipitate was filtered in a Buchner funnel. The solid was washed with water, washed with hexane, and dried under high vacuum to yield the intermediate compound (179 mg, 72% yield). To a N2-purged flask resulting in a yellow precipitate the solid precipitate was filtered in a Buchner funnel The solid was washed with water washed with hexane dried under high vacuum

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

Procedure: To a flask was added vanillin (3.28 g, 21.6 mmol) and 2-bromoethyl methyl ether (3.04 mL, 1.5 equiv) in a solution of DMF (20 mL). K2CO3 (5.5 g, 2 equiv) was then added to the solution and the reaction slurry was stirred at 90° C. for 16 h under N2. The reaction solution was diluted with EtOAc (100 mL), filtered, washed with sat NH4Cl, dried over Na2SO4, filtered and concentrated in vacuo. The crude material was chromatographed (SiO2, Hex/EtOAc 100:D to 70:30) to afford the intermediate compound. filtered washed with sat NH4Cl dried over Na2SO4 filtered concentrated in vacuo The crude material was chromatographed (SiO2, Hex/EtOAc 100:D to 70:30) to afford the intermediate compound

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

Conditions: temp:130.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 3-methoxy-4-(2-methoxyethoxy)benzaldehyde (10 g) in AcOH (80 mL) was added KOAc (9.5 g) and NH2OH.HCl (6.7 g). The resulting mixture was heated at 130° C. for 18 h under N2 atmospheres. After reaction finished, the mixture was poured into water (400 mL). The solid was collected, washed with water (100 mL) and air-dried to give 3-methoxy-4-(2-methoxyethoxy)benzonitrile (9 g) as a light yellow solid. 1H-NMR (400 MHz, CDCl3): δ: 7.26 (dd, J=8.4, 1.6, 1H), 7.08 (d, J=1.6, 1H), 6.93 (d, J=8.4, 1H), 4.23-4.20 (m, 2H), 3.88 (s, 3H), 3.82-3.80 (m, 2H), 3.45 (s, 3H). After reaction The solid was collected washed with water (100 mL) air-dried

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 3-methoxy-4-hydroxybenzaldehyde (8.0 g) in DMF (60 mL) was added K2CO3 (8.0 g) and 1-chloro-2-methoxyethane (5.1 g). The resulting mixture was stirred at 80° C. overnight. After reaction finished, ethyl acetate (200 mL) was added, and washed with 2 N aqueous HCl solution, brine, dried over Na2SO4, filtered, concentrated. The residue was washed with petrol ether to give 3-methoxy-4-(2-methoxyethoxy)benzaldehyde (10 g) as a yellow solid. 1H-NMR (400 MHz, CDCl3): δ: 9.86 (s, 1H); 7.45-7.41 (m, 2H); 7.01 (d, J=8.0, 1H); 4.27-4.25 (m, 2H); 3.93 (s, 3H); 3.85-3.82 (m, 2H); 3.46 (s, 3H). After reaction washed with 2 N aqueous HCl solution, brine dried over Na2SO4 filtered concentrated The residue was washed with petrol ether

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

Procedure: To a N2-purged flask was added 3-methoxy-4-(2-methoxy-ethoxy)-benzaldehyde from Step A (162 mg, 771 mmol), rhodanine (103 mg, 1 equiv), NaOAc (190 mg, 2.31 mmol) and HOAc (3 mL). The mixture was stirred and heated at 90° C. for 14 h under a condenser, resulting in a yellow precipitate. The reaction mixture was diluted with water (100 mL) and the solid precipitate was filtered in a Buchner funnel. The solid was washed with water, washed with hexane, and dried under high vacuum to yield the intermediate compound (179 mg, 72% yield). To a N2-purged flask resulting in a yellow precipitate the solid precipitate was filtered in a Buchner funnel The solid was washed with water washed with hexane dried under high vacuum

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

Procedure: To a flask was added vanillin (3.28 g, 21.6 mmol) and 2-bromoethyl methyl ether (3.04 mL, 1.5 equiv) in a solution of DMF (20 mL). K2CO3 (5.5 g, 2 equiv) was then added to the solution and the reaction slurry was stirred at 90° C. for 16 h under N2. The reaction solution was diluted with EtOAc (100 mL), filtered, washed with sat NH4Cl, dried over Na2SO4, filtered and concentrated in vacuo. The crude material was chromatographed (SiO2, Hex/EtOAc 100:D to 70:30) to afford the intermediate compound. filtered washed with sat NH4Cl dried over Na2SO4 filtered concentrated in vacuo The crude material was chromatographed (SiO2, Hex/EtOAc 100:D to 70:30) to afford the intermediate compound