6-bromo-2-hydroxy-3-methoxybenzaldehyde

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 6-bromo-2-hydroxy-3-methoxy-benzaldehyde (2.31 g, 10.0 mmol), neopentyl glycol (1.14 g, 11.0 mmol), TsOH (9.5 mg) and triethyl orthoformate (1.93 g, 13.0 mmol) were heated at 110° C. for 30 min and then partitioned between NaHCO3 (300 mL) solution and EtOAc (200 mL). The aqueous layer was extracted with EtOAc (3×30 mL) and the combined extracts were washed with brine and dried through Na2SO4. Evaporation of solvent afforded the title compound (3.17 g, 100%). 1H NMR (CDCl3) δ 0.85 (s, 3H), 1.27 (s, 3H), 3.70 (s, 2H), 3.82 (s, 2H), 3.85 (s, 3H), 5.90 (s, 1H), 6.72 (d, J=8 Hz, 1H), 7.02 (d, J=8 Hz, 1H). partitioned between NaHCO3 (300 mL) solution and EtOAc (200 mL) The aqueous layer was extracted with EtOAc (3×30 mL) the combined extracts were washed with brine dried through Na2SO4 Evaporation of solvent

反応条件: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 6-bromo-2-hydroxy-3-methoxy-benzaldehyde (2.31 g, 10.0 mmol), neopentyl glycol (1.14 g, 11.0 mmol), TsOH (9.5 mg) and triethyl orthoformate (1.93 g, 13.0 mmol) were heated at 110° C. for 30 min and then partitioned between NaHCO3 (300 mL) solution and EtOAc (200 mL). The aqueous layer was extracted with EtOAc (3×30 mL) and the combined extracts were washed with brine and dried through Na2SO4. Evaporation of solvent afforded the title compound (3.17 g, 100%). 1H NMR (CDCl3) δ 0.85 (s, 3H), 1.27 (s, 3H), 3.70 (s, 2H), 3.82 (s, 2H), 3.85 (s, 3H), 5.90 (s, 1H), 6.72 (d, J=8 Hz, 1H), 7.02 (d, J=8 Hz, 1H). partitioned between NaHCO3 (300 mL) solution and EtOAc (200 mL) The aqueous layer was extracted with EtOAc (3×30 mL) the combined extracts were washed with brine dried through Na2SO4 Evaporation of solvent

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 6-Bromo-2-hydroxy-3-methoxybenzaldehyde (2.00 g, 8.65 mmol) was dissolved in methylene chloride (10 mL) and cooled to 0° C. Boron tribromide (17.0 mL of a 1.0 M solution, 17.00 mmol) was added by syringe and the solution was stirred at 0° C. for 1 h before allowing the reaction to warm up to ambient temperature and stir for 15 h at which time TLC analysis indicated the reaction complete. The reaction mixture was poured onto ice and extracted with ethyl acetate. The organic layers were dried with magnesium sulfate and concentrated by rotary evaporation to afford 1.82 g of 6-bromo-2,3-dihydroxybenzaldehyde (8.39 mmol, 97% yield) as a yellow solid. the reaction to warm up to ambient temperature stir for 15 h at which time TLC analysis The reaction mixture was poured onto ice extracted with ethyl acetate The organic layers were dried with magnesium sulfate concentrated by rotary evaporation

反応条件: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 6-bromo-2-hydroxy-3-methoxy-benzaldehyde (2.31 g, 10.0 mmol), neopentyl glycol (1.14 g, 11.0 mmol), TsOH (9.5 mg) and triethyl orthoformate (1.93 g, 13.0 mmol) were heated at 110° C. for 30 min and then partitioned between NaHCO3 (300 mL) solution and EtOAc (200 mL). The aqueous layer was extracted with EtOAc (3×30 mL) and the combined extracts were washed with brine and dried through Na2SO4. Evaporation of solvent afforded the title compound (3.17 g, 100%). 1H NMR (CDCl3) δ 0.85 (s, 3H), 1.27 (s, 3H), 3.70 (s, 2H), 3.82 (s, 2H), 3.85 (s, 3H), 5.90 (s, 1H), 6.72 (d, J=8 Hz, 1H), 7.02 (d, J=8 Hz, 1H). partitioned between NaHCO3 (300 mL) solution and EtOAc (200 mL) The aqueous layer was extracted with EtOAc (3×30 mL) the combined extracts were washed with brine dried through Na2SO4 Evaporation of solvent

反応条件: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 6-bromo-2-hydroxy-3-methoxy-benzaldehyde (2.31 g, 10.0 mmol), neopentyl glycol (1.14 g, 11.0 mmol), TsOH (9.5 mg) and triethyl orthoformate (1.93 g, 13.0 mmol) were heated at 110° C. for 30 min and then partitioned between NaHCO3 (300 mL) solution and EtOAc (200 mL). The aqueous layer was extracted with EtOAc (3×30 mL) and the combined extracts were washed with brine and dried through Na2SO4. Evaporation of solvent afforded the title compound (3.17 g, 100%). 1H NMR (CDCl3) δ 0.85 (s, 3H), 1.27 (s, 3H), 3.70 (s, 2H), 3.82 (s, 2H), 3.85 (s, 3H), 5.90 (s, 1H), 6.72 (d, J=8 Hz, 1H), 7.02 (d, J=8 Hz, 1H). partitioned between NaHCO3 (300 mL) solution and EtOAc (200 mL) The aqueous layer was extracted with EtOAc (3×30 mL) the combined extracts were washed with brine dried through Na2SO4 Evaporation of solvent

反応条件: temp:22.01; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 6-bromo-2-hydroxy-3-methoxy-benzaldehyde (2.31 g, 10.0 mmol), neopentyl glycol (1.14 g, 11.0 mmol), TsOH (9.5 mg) and triethyl orthoformate (1.93 g, 13.0 mmol) were heated at 110° C. for 30 min and then partitioned between NaHCO3 (300 mL) solution and EtOAc (200 mL). The aqueous layer was extracted with EtOAc (3×30 mL) and the combined extracts were washed with brine and dried through Na2SO4. Evaporation of solvent afforded the title compound (3.17 g, 100%). 1H NMR (CDCl3) δ 0.85 (s, 3H), 1.27 (s, 3H), 3.70 (s, 2H), 3.82 (s, 2H), 3.85 (s, 3H), 5.90 (s, 1H), 6.72 (d, J=8 Hz, 1H), 7.02 (d, J=8 Hz, 1H). partitioned between NaHCO3 (300 mL) solution and EtOAc (200 mL) The aqueous layer was extracted with EtOAc (3×30 mL) the combined extracts were washed with brine dried through Na2SO4 Evaporation of solvent

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 6-bromo-2-hydroxy-3-methoxybenzaldehyde (66.8 g, 0.29 mole), K2CO3 (powdered, 79 g, 0.57 mole), and dry DMF (250 mL) was stirred under N2 at 110° as dimethylsulfate (33.5 mL, 0.35 mole) was added dropwise. The reaction mixture was stirred at 135° for 5 hours, was cooled to room temperature, and water was added. The aqueous mixture was extracted with CH2Cl2. The combined extracts were washed with water, saturated aqueous NaCl, dried (MgSO4), filtered, and evaporated to yield ca 80 g. tan solid. The crude product was recrystallized from 2-propanol to obtain 55.2 g cream colored solid, (77%); mp 92°-3°. was added dropwise The aqueous mixture was extracted with CH2Cl2 The combined extracts were washed with water, saturated aqueous NaCl dried (MgSO4) filtered evaporated to yield ca 80 g The crude product was recrystallized from 2-propanol to obtain 55.2 g cream colored solid, (77%)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 3-bromo-2-formyl-6-methoxyphenylmethyl carbonate (100 g, 0.34 mole), 500 mL 10% aqueous NaOH, and 2 L MeOH was stirred at reflux for 2 hours. After cooling to room temperature, the MeOH was removed (in-vacuo). The aqueous solution was cooled to 0° and acidified with concentrated HCl. The solid was filtered, washed with water, and dried (in-vacuo) to yield 107 g yellow solid which was recrystallized from 2-propanol to yield 62 g yellow solid; mp 95°-6°; M+ 230. at reflux for 2 hours the MeOH was removed (in-vacuo) The aqueous solution was cooled to 0° The solid was filtered washed with water dried (in-vacuo)

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred solution of 6-bromo-2-hydroxy-3-methoxybenzaldehyde (0.33 g, 1.43 mmol) and triethylamine (0.17 g, 1.71 mmol) in dichloromethane (5 mL) was added methanesulfonyl chloride (0.19 g, 2.3 mmol) at 0° C., the reaction was stirred at 0° C. for 10 minutes and then at room temperature for 30 minutes, by which time a brown colour had developed. Water (20 mL) was added, the mixture was extracted with ethyl acetate (2×20 mL). The combined extract was washed with brine, dried over MgSO4, filtered and evaporated to give a crude solid (0.42 g). Flash chromatography over silica gel (60 g), eluting with hexane-ethyl acetate (3:1), gave 3-bromo-2-formyl-6-methoxyphenyl methanesulfonate (320 mg, 72%) and 5-bromo-8-methoxybenzo[e][1,2]oxathiine 2,2-dioxide (90 mg, 22%) as white solids. The 3-bromo-2-formyl-6-methoxyphenyl methanesulfonate had m.p. 95-97° C.; NMR Spectrum δH (300 MHz, CDCl3) 10.30 (1H, s, CHO), 7.58 (1H, d, J 8.9 Hz, 4-H), 7.11 (1H, d, J 8.9 Hz, 5-H), 3.95 (3H, s, OCH3), 3.57 (3H, s, SCH3); NMR Spectrum δC (75 MHz, CDCl3) 40.4, 57.1, 115.5, 118.3, 129.2, 133.2, 138.9, 152.9, 190.0; νmax/cm−1 (thin film) 1705, 1565, 1468, 1399, 1363, 1293, 1219, 1165, 1130, 971, 878, 800; m/z (ES) 374/372 (MNa2H2O+, 100%), 333/331 (MNa+, 80); Rf (hexane-ethyl acetate 1:1) 0.35. The 5-bromo-8-methoxybenzo[e][1,2]oxathiine 2,2-dioxide had m.p. 186-188° C.; Elemental Analysis Found: C, 37.3; H, 2.2; S, 10.9; Br, 27.2 (C9H7BrO4S requires C, 37.13; H, 2.42; S, 11.01; Br, 27.45%); NMR Spectrum δH (300 MHz, CDCl3) 7.62 (1H, d, J 10.5 Hz, 4-H), 7.47 (1H, d, J 10.5 Hz, 6-H), 6.96 (1H, d, J 10.5 Hz, 7-H), 6.88 (1H, d, J 10.5 Hz, 3-H), 3.88 (3H, s, OCH3); NMR Spectrum δC (75 MHz, CDCl3) 57.0, 113.7, 116.2, 120.3; 123.9, 129.9, 135.8, 142.0, 149.1; νmax/cm−1 (nujol mull) 3091, 2959, 2924, 2854, 1608, 1569, 1468, 1367, 1309, 1270, 1169, 1080, 909; Rf(hexane-ethyl acetate 1:1) 0.60. at room temperature for 30 minutes the mixture was extracted with ethyl acetate (2×20 mL) The combined extract was washed with brine dried over MgSO4 filtered evaporated to give a crude solid (0.42 g) Flash chromatography over silica gel (60 g), eluting with hexane-ethyl acetate (3:1)