3-methoxy-4-propan-2-yloxybenzaldehyde

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Carbon tetrabromide (51.3 g, 154.7 mmol) was added portion-wise to a magnetically stirred mixture of zinc dust (0.1 g, 154.5 mmol) and PP3 (40.5 g, 159.4 mmol) in CH2Cl2 (350 ml) maintained at 0° C. on an ice-salt bath. This suspension was allowed to warm to room temperature and then stirred at for a further 22 h. After this time the reaction mixture was re-cooled to 0° C. and vanillin isopropyl ether (15.0 g, 77.3 mmol) was added dropwise over 2 min. and allowed to stir at room temperature for 1 h. After dilution with hexane (200 ml) the resulting mixture was filtered through a sintered glass funnel and the filtrate concentrated on to silica gel (30 g). The resulting solid was added to the top of a flash chromatography column (silica gel: 20 cm long×10 cm wide) which was subjected to gradient elution (2:1, 1:1 and then 1:2 hexane/CH2Cl2). Concentration of the appropriate fractions (Rf 0.5 in 1:1 hexane/CH2Cl2) then afforded the title compound (27.2 g, 99.8%) as white crystalline masses, m.p. 36-38° C. IR(KBr disc, cm−1) 2976, 2973, 1599, 1510.1464, 1418, 1383, 1373, 1267, 1235, 1141, 1110, 1036. 1H NMR (300 MHz, CDCl3) δ7.41 (s, 1H), 7.21 (d, J=2.1 Hz, 1H), 7.07 (dd, J=2.1, 8.4 Hz, 1H), 6.87 (d, J=8.4 Hz), 4.58 (septet J=6.0 Hz, 1H), 3.87 (s, 3H), 1.39 (d, J=6.0 Hz, 6H). 13C NMR+APT (75.5 MHz, CDCl3) δ149.7 (C), 147.7 (C), 136.5 (CH), 127.9 (C), 121.9 (CH), 114.4 (CH), 111.8 (CH), 87.1 (CH), 71.1 (CH), 56.0 (CH3), 22.1 (CH3). MS (70 eV) m/z(%): 352 (28), 350 (49), 448 (31) (M+•), 310 (51), 308 (100), 306 (54) M+•−CH2CHCH3), 295 (34), 293 (38), 291 (36) (M+•−CH2CHCH3—CH). Anal. Calcd for C12H14O2Br2, 41.17; H. 4.03; Br, 45.65. Found: C, 41.21; H, 3.92; Br, 45.47. to warm to room temperature After this time the reaction mixture was re-cooled to 0° C. to stir at room temperature for 1 h After dilution with hexane (200 ml) the resulting mixture was filtered through a sintered glass funnel the filtrate concentrated on to silica gel (30 g) The resulting solid was added to the top of a flash chromatography column (silica gel 20 cm long×10 cm wide) which was subjected to gradient elution (2:1, 1:1

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Carbon tetrabromide (51.3 g, 154.7 mmol) was added portion-wise to a magnetically stirred mixture of zinc dust (0.1 g, 154.5 mmol) and PP3 (40.5 g, 159.4 mmol) in CH2Cl2 (350 ml) maintained at 0° C. on an ice-salt bath. This suspension was allowed to warm to room temperature and then stirred at for a further 22 h. After this time the reaction mixture was re-cooled to 0° C. and vanillin isopropyl ether (15.0 g, 77.3 mmol) was added dropwise over 2 min. and allowed to stir at room temperature for 1 h. After dilution with hexane (200 ml) the resulting mixture was filtered through a sintered glass funnel and the filtrate concentrated on to silica gel (30 g). The resulting solid was added to the top of a flash chromatography column (silica gel: 20 cm long×10 cm wide) which was subjected to gradient elution (2:1, 1:1 and then 1:2 hexane/CH2Cl2). Concentration of the appropriate fractions (Rf 0.5 in 1:1 hexane/CH2Cl2) then afforded the title compound (27.2 g, 99.8%) as white crystalline masses, m.p. 36-38° C. IR(KBr disc, cm−1) 2976, 2973, 1599, 1510.1464, 1418, 1383, 1373, 1267, 1235, 1141, 1110, 1036. 1H NMR (300 MHz, CDCl3) δ7.41 (s, 1H), 7.21 (d, J=2.1 Hz, 1H), 7.07 (dd, J=2.1, 8.4 Hz, 1H), 6.87 (d, J=8.4 Hz), 4.58 (septet J=6.0 Hz, 1H), 3.87 (s, 3H), 1.39 (d, J=6.0 Hz, 6H). 13C NMR+APT (75.5 MHz, CDCl3) δ149.7 (C), 147.7 (C), 136.5 (CH), 127.9 (C), 121.9 (CH), 114.4 (CH), 111.8 (CH), 87.1 (CH), 71.1 (CH), 56.0 (CH3), 22.1 (CH3). MS (70 eV) m/z(%): 352 (28), 350 (49), 448 (31) (M+•), 310 (51), 308 (100), 306 (54) M+•−CH2CHCH3), 295 (34), 293 (38), 291 (36) (M+•−CH2CHCH3—CH). Anal. Calcd for C12H14O2Br2, 41.17; H. 4.03; Br, 45.65. Found: C, 41.21; H, 3.92; Br, 45.47. to warm to room temperature After this time the reaction mixture was re-cooled to 0° C. to stir at room temperature for 1 h After dilution with hexane (200 ml) the resulting mixture was filtered through a sintered glass funnel the filtrate concentrated on to silica gel (30 g) The resulting solid was added to the top of a flash chromatography column (silica gel 20 cm long×10 cm wide) which was subjected to gradient elution (2:1, 1:1

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

Procedure: Isopropyl bromide (40.0 mL, 421 mmol) was added to a suspension of K2CO3 (48.0 g, 348 mmol) and vanillin (40 g, 263 mmol) in DMF (150 mL) and the stirring slurry heated to 80° C. for 15 h. The reaction mixture was then cooled to room temperature, diluted with diethyl ether (200 mL) and washed with H2O (4×200 mL), dried (MgSO4) and concentrated under reduced pressure giving the title compound as a slightly tan oil (51.0 g, 100%) which required no further purification. The spectra of this material are identical with that previously reported (M. F. Comber and M. V. Sargent, J. Chem. Soc., Perkin Trans. 1, 1991, 2783). The reaction mixture was then cooled to room temperature washed with H2O (4×200 mL) dried (MgSO4) concentrated under reduced pressure

Conditions: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 4-hydroxy-3-methoxybenzaldehyde (100 g), anhydrous potassium carbonate (182 g) and 2-bromopropane (81 ml) in DMF (500 ml) was stirred at 65° C. for 2 h. The reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with water and brine. The organic layer was dried (MgSO4), filtered and concentrated in vacuo. extracted with ethyl acetate The organic layer was washed with water and brine The organic layer was dried (MgSO4) filtered concentrated in vacuo

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Carbon tetrabromide (51.3 g, 154.7 mmol) was added portion-wise to a magnetically stirred mixture of zinc dust (10.1 g, 154.5 mmol) and PPh3 (40.5 g, 159.4 mmol) in CH2Cl2 (350 ml) maintained at 0° C. on an ice-salt bath. This suspension was allowed to warm to room temperature and then stirred at for a further 22 h. After this time the reaction mixture was re-cooled to 0° C. and vanillin isopropyl ether (15.0 g, 77.3 mmol) was added dropwise over 2 min. and allowed to stir at room temperature for 1 h. After dilution with hexane (200 ml) the resulting mixture was filtered through a sintered glass funnel and the filtrate concentrated on to silica gel (30 g). The resulting solid was added to the top of a flash chromatography column (silica gel: 20 cm long×10 cm wide) which was subjected to gradient elution (2:1, 1:1 and then 1:2 hexane/CH2Cl2). Concentration of the appropriate fractions (Rf 0.5 in 1:1 hexane/CH2Cl2) then afforded the title compound (27.2 g, 99.8%) as white crystalline masses, m.p. 36-38° C. IR (KBr disc, cm−1) 2976, 2973, 1599, 1510, 1464, 1418, 1383, 1373, 1267, 1235, 1141, 1110, 1036. 1H NMR (300 MHz, CDCl3) δ 7.41 (s, 1H), 7.21 (d, J=2.1 Hz, 1H), 7.07 (dd, J=2.1, 8.4 Hz, 1H), 6.87 (d, J=8.4 Hz), 4.58 (septet, J=6.0 Hz, 1H), 3.87 (s, 3H), 1.39 (d, J=6.0 Hz, 6H). 13C NMR+APT (75.5 MHz, CDCl3) δ 149.7 (C), 147.7 (C), 136.5 (CH), 127.9 (C), 121.9 (CH), 114.4 (CH), 111.8 (CH), 87.1 (CH), 71.1 (CH), 56.0 (CH3), 22.1 (CH3). MS (70 eV) m/z (%): 352 (28), 350 (49), 448 (31) (M+·), 310 (51), 308 (100), 306 (54) (M+·-CH2CHCH3), 295 (34), 293 (38), 291 (36) (M+·-CH2CHCH3—CH3). Anal. Calcd for C12H14O2Br2, 41.17; H, 4.03; Br, 45.65. Found: C, 41.21; H, 3.92; Br, 45.47. to warm to room temperature After this time the reaction mixture was re-cooled to 0° C. to stir at room temperature for 1 h After dilution with hexane (200 ml) the resulting mixture was filtered through a sintered glass funnel the filtrate concentrated on to silica gel (30 g) The resulting solid was added to the top of a flash chromatography column (silica gel 20 cm long×10 cm wide) which was subjected to gradient elution (2:1, 1:1

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

Procedure: Isopropyl bromide (40.0 mL, 421 mmol) was added to a suspension of K2CO3 (48.0 g, 348 mmol) and vanillin (40 g, 263 mmol) in DMF (150 mL) and the stirring slurry heated to 80° C. for 15 h. The reaction mixture was then cooled to room temperature, diluted with diethyl ether (200 mL) and washed with H2O (4×200 mL), dried (MgSO4) and concentrated under reduced pressure giving the title compound as a slightly tan oil (51.0 g, 100%) which required no further purification. The spectra of this material are identical with that previously reported (M. F. Comber and M. V. Sargent, J. Chem. Soc., Perkin Trans. 1, 1991, 2783). The reaction mixture was then cooled to room temperature washed with H2O (4×200 mL) dried (MgSO4) concentrated under reduced pressure

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Carbon tetrabromide (51.3 g, 154.7 mmol) was added portion-wise to a magnetically stirred mixture of zinc dust (10.1 g, 154.5 mmol) and PPh3 (40.5 g, 159.4 mmol) in CH2Cl2 (350 ml) maintained at 0° C. on an ice-salt bath. This suspension was allowed to warm to room temperature and then stirred at for a further 22 h. After this time the reaction mixture was re-cooled to 0° C. and vanillin isopropyl ether (15.0 g, 77.3 mmol) was added dropwise over 2 min. and allowed to stir at room temperature for 1 h. After dilution with hexane (200 ml) the resulting mixture was filtered through a sintered glass funnel and the filtrate concentrated on to silica gel (30 g). The resulting solid was added to the top of a flash chromatography column (silica gel: 20 cm long×10 cm wide) which was subjected to gradient elution (2:1, 1:1 and then 1:2 hexane/CH2Cl2). Concentration of the appropriate fractions (Rf 0.5 in 1:1 hexane/CH2Cl2) then afforded the title compound (27.2 g, 99.8%) as white crystalline masses, m.p. 36-38° C. IR (KBr disc, cm−1) 2976, 2973, 1599, 1510, 1464, 1418, 1383, 1373, 1267, 1235, 1141, 1110, 1036. 1H NMR (300 MHz, CDCl3) δ 7.41 (s, 1H), 7.21 (d, J=2.1 Hz, 1H), 7.07 (dd, J=2.1, 8.4 Hz, 1H), 6.87 (d, J=8.4 Hz), 4.58 (septet, J=6.0 Hz, 1H), 3.87 (s, 3H), 1.39 (d, J=6.0 Hz, 6H). 13C NMR+APT (75.5 MHz, CDCl3) δ 149.7 (C), 147.7 (C), 136.5 (CH), 127.9 (C), 121.9 (CH), 114.4 (CH), 111.8 (CH), 87.1 (CH), 71.1 (CH), 56.0 (CH3), 22.1 (CH3). MS (70 eV) m/z (%): 352 (28), 350 (49), 448 (31) (M+·), 310 (51), 308 (100), 306 (54) (M+·-CH2CHCH3), 295 (34), 293 (38), 291 (36) (M+·-CH2CHCH3—CH3). Anal. Calcd for C12H14O2Br2, 41.17; H, 4.03; Br, 45.65. Found: C, 41.21; H, 3.92; Br, 45.47. to warm to room temperature After this time the reaction mixture was re-cooled to 0° C. to stir at room temperature for 1 h After dilution with hexane (200 ml) the resulting mixture was filtered through a sintered glass funnel the filtrate concentrated on to silica gel (30 g) The resulting solid was added to the top of a flash chromatography column (silica gel 20 cm long×10 cm wide) which was subjected to gradient elution (2:1, 1:1

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

Procedure: Isopropyl bromide (40.0 mL, 421 mmol) was added to a suspension of K2CO3 (48.0 g, 348 mmol) and vanillin (40 g, 263 mmol) in DMF (150 mL) and the stirring slurry heated to 80° C. for 15 h. The reaction mixture was then cooled to room temperature, diluted with diethyl ether (200 mL) and washed with H2O (4×200 mL), dried (MgSO4) and concentrated under reduced pressure giving the title compound as a slightly tan oil (51.0 g, 100%) which required no further purification. The spectra of this material are identical with that previously reported (M. F. Comber and M. V. Sargent, J. Chem. Soc., Perkin Trans. 1, 1991, 2783). The reaction mixture was then cooled to room temperature washed with H2O (4×200 mL) dried (MgSO4) concentrated under reduced pressure

Conditions: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 4-hydroxy-3-methoxybenzaldehyde (100 g), potassium carbonate (182 g) and 2-bromopropane (81 ml) in DMF (500 ml) was stirred at 65° C. for 2 h. The reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with water and brine. The organic layer was dried (MgSO4), filtered and concentrated in vacuo. extracted with ethyl acetate The organic layer was washed with water and brine The organic layer was dried (MgSO4) filtered concentrated in vacuo

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Carbon tetrabromide (51.3 g, 154.7 mmol) was added portion-wise to a magnetically stirred mixture of zinc dust (10.1 g, 154.5 mmol) and PPh3 (40.5 g, 159.4 mmol) in CH2Cl2 (350 ml) maintained at 0° C. on an ice-salt bath. This suspension was allowed to warm to room temperature and then stirred at for a further 22 h. After this time the reaction mixture was re-cooled to 0° C. and vanillin isopropyl ether (15.0 g, 77.3 mmol) was added dropwise over 2 min. and allowed to stir at room temperature for 1 h. After dilution with hexane (200 ml) the resulting mixture was filtered through a sintered glass funnel and the filtrate concentrated on to silica gel (30 g). The resulting solid was added to the top of a flash chromatography column (silica gel: 20 cm long×10 cm wide) which was subjected to gradient elution (2:1, 1:1 and then 1:2 hexane/CH2Cl2). Concentration of the appropriate fractions (Rf 0.5 in 1:1 hexane/CH2Cl2) then afforded the title compound (27.2 g, 99.8%) as white crystalline masses, m.p. 36–38° C. IR (KBr disc, cm−1) 2976, 2973, 1599, 1510, 1464, 1418, 1383, 1373, 1267, 1235, 1141, 1110, 1036. 1H NMR (300 MHz, CDCl3) δ 7.41 (s, 1H), 7.21 (d, J=2.1 Hz, 1H), 7.07 (dd, J=2.1, 8.4 Hz, 1H), 6.87 (d, J=8.4 Hz), 4.58 (septet, J=6.0 Hz, 1H), 3.87 (s, 3H), 1.39 (d, J=6.0 Hz, 6H). 13C NMR+APT (75.5 MHz, CDCl3) δ 149.7 (C), 147.7 (C), 136.5 (CH), 127.9 (C), 121.9 (CH), 114.4 (CH), 111.8 (CH), 87.1 (CH), 71.1 (CH), 56.0 (CH3), 22.1 (CH3). MS (70 eV) m/z (%): 352 (28), 350 (49), 448 (31) (M+•), 310 (51), 308 (100), 306 (54) (M+•-CH2CHCH3), 295 (34), 293 (38), 291 (36) (M+•-CH2CHCH3—CH3). Anal. Calcd for C12H14O2Br2, 41.17; H, 4.03; Br, 45.65. Found: C, 41.21; H, 3.92; Br, 45.47. to warm to room temperature After this time the reaction mixture was re-cooled to 0° C. to stir at room temperature for 1 h After dilution with hexane (200 ml) the resulting mixture was filtered through a sintered glass funnel the filtrate concentrated on to silica gel (30 g) The resulting solid was added to the top of a flash chromatography column (silica gel 20 cm long×10 cm wide) which was subjected to gradient elution (2:1, 1:1

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

Procedure: Isopropyl bromide (40.0 mL; 421 mmol) was added to a suspension of K2CO3 (48.0 g, 348 mmol) and vanillin (40 g, 263 mmol) in DMF (150 mL) and the stirring slurry heated to 80° C. for 15 h. The reaction mixture was then cooled to room temperature, diluted with diethyl ether (200 mL) and washed with H2O (4×200 mL), dried (MgSO4) and concentrated under reduced pressure giving the title compound as a slightly tan oil (51.0 g, 100%) which required no further purification. The spectra of this material are identical with that previously reported (M. F. Comber and M. V. Sargent, J. Chem. Soc., Perkin Trans. 1, 1991, 2783). The reaction mixture was then cooled to room temperature washed with H2O (4×200 mL) dried (MgSO4) concentrated under reduced pressure

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Carbon tetrabromide (51.3 g, 154.7 mmol) was added portion-wise to a magnetically stirred mixture of zinc dust (0.1 g, 154.5 mmol) and PP3 (40.5 g, 159.4 mmol) in CH2Cl2 (350 ml) maintained at 0° C. on an ice-salt bath. This suspension was allowed to warm to room temperature and then stirred at for a further 22 h. After this time the reaction mixture was re-cooled to 0° C. and vanillin isopropyl ether (15.0 g, 77.3 mmol) was added dropwise over 2 min. and allowed to stir at room temperature for 1 h. After dilution with hexane (200 ml) the resulting mixture was filtered through a sintered glass funnel and the filtrate concentrated on to silica gel (30 g). The resulting solid was added to the top of a flash chromatography column (silica gel: 20 cm long×10 cm wide) which was subjected to gradient elution (2:1, 1:1 and then 1:2 hexane/CH2Cl2). Concentration of the appropriate fractions (Rf 0.5 in 1:1 hexane/CH2Cl2) then afforded the title compound (27.2 g, 99.8%) as white crystalline masses, m.p. 36-38° C. IR(KBr disc, cm−1) 2976, 2973, 1599, 1510.1464, 1418, 1383, 1373, 1267, 1235, 1141, 1110, 1036. 1H NMR (300 MHz, CDCl3) δ7.41 (s, 1H), 7.21 (d, J=2.1 Hz, 1H), 7.07 (dd, J=2.1, 8.4 Hz, 1H), 6.87 (d, J=8.4 Hz), 4.58 (septet J=6.0 Hz, 1H), 3.87 (s, 3H), 1.39 (d, J=6.0 Hz, 6H). 13C NMR+APT (75.5 MHz, CDCl3) δ149.7 (C), 147.7 (C), 136.5 (CH), 127.9 (C), 121.9 (CH), 114.4 (CH), 111.8 (CH), 87.1 (CH), 71.1 (CH), 56.0 (CH3), 22.1 (CH3). MS (70 eV) m/z(%): 352 (28), 350 (49), 448 (31) (M+•), 310 (51), 308 (100), 306 (54) M+•−CH2CHCH3), 295 (34), 293 (38), 291 (36) (M+•−CH2CHCH3—CH). Anal. Calcd for C12H14O2Br2, 41.17; H. 4.03; Br, 45.65. Found: C, 41.21; H, 3.92; Br, 45.47. to warm to room temperature After this time the reaction mixture was re-cooled to 0° C. to stir at room temperature for 1 h After dilution with hexane (200 ml) the resulting mixture was filtered through a sintered glass funnel the filtrate concentrated on to silica gel (30 g) The resulting solid was added to the top of a flash chromatography column (silica gel 20 cm long×10 cm wide) which was subjected to gradient elution (2:1, 1:1