2,2-二甲基-3,4-二氢-2H-1-苯并吡喃-7-醇

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: In a 250 mL round-bottom flask was placed 2,2-dimethyl-Chroman-7-ol (1.76 g, 9.87 mmol, from Step 4-1-2) in 30 mL of dry dichloroethane under argon. The solution was cooled to 0° C. where boron trichloride (10.8 mL, 1M in CH2Cl2, 10.8 mmol, 1.1 eq) was added dropwise. At this point, methyl thiocyanate (0.80 g, 10.8 mmol, 1.1 eq) was added followed by aluminum trichloride (1.32 g, 9.87 mmol, 1 eq). The reaction was allowed to warm up to rt and stirred for 17 h. The reaction mixture was cooled down to 0° C. and 10 mL of 50% w/w NaOH was added to adjust the solution to PH—14, followed by 40 mL of water. The solution was then refluxed at 65° C. for 2 h. The solution was allowed to cool to ambient temperature. The aqueous layer was washed with dichloromethane (20 mL). The aqueous solution was transferred to an Erlenmeyer flask and acidified to pH˜1 with conc. HCl. This solution was then extracted with EtOAc (3×20 mL) and the combined organic layers were dried over Na2SO4, filtered and evaporated. The residue was purified on silica gel (flash column chromatography) eluting with 5% ethyl acetate-hexane followed by 20% ethyl acetate-hexane to provide the desired product as white solid. The desired product was white solid (0.33 g, 16.5%). 1H-NMR (CD3CN) δ 7.93 (broad s, 1H, OH), 7.26 (s, 1H), 6.28 (s, 1H), 2.69 (t, 2H), 1.80 (t, 2H), 1.32 (s, 6H). In a 250 mL round-bottom flask was placed was added dropwise The reaction mixture was cooled down to 0° C. The solution was then refluxed at 65° C. for 2 h to cool to ambient temperature The aqueous layer was washed with dichloromethane (20 mL) This solution was then extracted with EtOAc (3×20 mL) the combined organic layers were dried over Na2SO4 filtered evaporated The residue was purified on silica gel (flash column chromatography) eluting with 5% ethyl acetate-hexane

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a stirred solution of 7-Methoxy-2,2-dimethyl-chroman (4.55 g, 23.7 mmol, from step 1) in anhydrous dichloromethane (50 mL) was added 1M BBr3 (72.86 mL, 47.4 mmol, 2.0 eq) via cannula over 10 min. The resulting dark brown solution was stirred at rt for 17 h. Saturated solution of NaHCO3 (50 mL) was added and extracted with CH2Cl2 (3×50 mL. The combined organic layers were dried over Na2SO4, filtered and evaporated. The residue was purified on silica gel (flash column chromatography) eluting with 5% ethyl acetate-hexane followed by 20% ethyl acetate-hexane to provide the desired product as white solid (1.76 g, 42%). 1H-NMR (CD3CN) δ 6.89 (d, J=8.5 Hz, 1H), 6.68 (broad, s, 1H, OH), 6.31 (dd, J=2.4, 8.5 Hz, 1H), 6.15 (d, J=2.4 Hz, 1H), 2.69 (t, 2H), 1.79 (t, 2H), 1.31 (s, 6H). MS LC-MS (MH+=179). extracted with CH2Cl2 (3×50 mL The combined organic layers were dried over Na2SO4 filtered evaporated The residue was purified on silica gel (flash column chromatography) eluting with 5% ethyl acetate-hexane

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a stirred solution of 7-Methoxy-2,2-dimethyl-chroman (4.55 g, 23.7 mmol, from step 1) in anhydrous dichloromethane (50 mL) was added 1M BBr3 (72.86 mL, 47.4 mmol, 2.0 eq) via cannula over 10 min. The resulting dark brown solution was stirred at rt for 17 h. Saturated solution of NaHCO3 (50 mL) was added and extracted with CH2Cl2 (3×50 mL. The combined organic layers were dried over Na2SO4, filtered and evaporated. The residue was purified on silica gel (flash column chromatography) eluting with 5% ethyl acetate-hexane followed by 20% ethyl acetate-hexane to provide the desired product as white solid (1.76 g, 42%). 1H-NMR (CD3CN) δ 6.89 (d, J=8.5 Hz, 1H), 6.68 (broad, s, 1H, OH), 6.31 (dd, J=2.4, 8.5 Hz, 1H), 6.15 (d, J=2.4 Hz, 1H), 2.69 (t, 2H), 1.79 (t, 2H), 1.31 (s, 6H). MS LC-MS (MH+=179). extracted with CH2Cl2 (3×50 mL The combined organic layers were dried over Na2SO4 filtered evaporated The residue was purified on silica gel (flash column chromatography) eluting with 5% ethyl acetate-hexane

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: In a 250 mL round-bottom flask was placed 2,2-dimethyl-Chroman-7-ol (1.76 g, 9.87 mmol, from Step 4-1-2) in 30 mL of dry dichloroethane under argon. The solution was cooled to 0° C. where boron trichloride (10.8 mL, 1M in CH2Cl2, 10.8 mmol, 1.1 eq) was added dropwise. At this point, methyl thiocyanate (0.80 g, 10.8 mmol, 1.1 eq) was added followed by aluminum trichloride (1.32 g, 9.87 mmol, 1 eq). The reaction was allowed to warm up to rt and stirred for 17 h. The reaction mixture was cooled down to 0° C. and 10 mL of 50% w/w NaOH was added to adjust the solution to PH˜14, followed by 40 mL of water. The solution was then refluxed at 65° C. for 2 h. The solution was allowed to cool to ambient temperature. The aqueous layer was washed with dichloromethane (20 mL). The aqueous solution was transferred to an Erlenmeyer flask and acidified to pH˜1 with conc. HCl. This solution was then extracted with EtOAc (3×20 mL) and the combined organic layers were dried over Na2SO4, filtered and evaporated. The residue was purified on silica gel (flash column chromatography) eluting with 5% ethyl acetate-hexane followed by 20% ethyl acetate-hexane to provide the desired product as white solid. The desired product was white solid (0.33 g, 16.5% ). 1H-NMR (CD3CN) δ 7.93 (broad s, 1H, OH), 7.26 (s, 1H), 6.28 (s, 1H), 2.69 (t, 2H), 1.80 (t, 2H), 1.32 (s, 6H). In a 250 mL round-bottom flask was placed was added dropwise The reaction mixture was cooled down to 0° C. The solution was then refluxed at 65° C. for 2 h to cool to ambient temperature The aqueous layer was washed with dichloromethane (20 mL) This solution was then extracted with EtOAc (3×20 mL) the combined organic layers were dried over Na2SO4 filtered evaporated The residue was purified on silica gel (flash column chromatography) eluting with 5% ethyl acetate-hexane

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a stirred solution of 7-Methoxy-2,2-dimethyl-chroman (4.55 g, 23.7 mmol, from step 1) in anhydrous dichloromethane (50 mL) was added 1M BBr3 (72.86 mL, 47.4 mmol, 2.0 eq ) via cannula over 10 min. The resulting dark brown solution was stirred at rt for 17 h. Saturated solution of NaHCO3 (50 mL) was added and extracted with CH2Cl2 (3×50 mL. The combined organic layers were dried over Na2SO4, filtered and evaporated. The residue was purified on silica gel (flash column chromatography) eluting with 5% ethyl acetate-hexane followed by 20% ethyl acetate-hexane to provide the desired product as white solid (1.76 g, 42%). 1H-NMR (CD3CN) δ 6.89 (d, J=8.5 Hz, 1H), 6.68 (broad, s, 1H, OH), 6.31 (dd, J=2.4, 8.5 Hz, 1H), 6.15 (d, J=2.4Hz, 1H ), 2.69 (t, 2H ), 1.79 (t, 2H), 1.31 (s, 6H). MS LC-MS (MH+=179). extracted with CH2Cl2 (3×50 mL The combined organic layers were dried over Na2SO4 filtered evaporated The residue was purified on silica gel (flash column chromatography) eluting with 5% ethyl acetate-hexane

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: In a 250 mL round-bottom flask was placed 2,2-dimethyl-Chroman-7-ol (1.76 g, 9.87 mmol, from Step 4-1-2) in 30 mL of dry dichloroethane under argon. The solution was cooled to 0° C. where boron trichloride (10.8 mL, 1M in CH2Cl2, 10.8 mmol, 1.1 eq) was added dropwise. At this point, methyl thiocyanate (0.80 g, 10.8 mmol, 1.1 eq) was added followed by aluminum trichloride (1.32 g, 9.87 mmol, 1 eq). The reaction was allowed to warm up to rt and stirred for 17 h. The reaction mixture was cooled down to 0° C. and 10 mL of 50% w/w NaOH was added to adjust the solution to PH˜14, followed by 40 mL of water. The solution was then refluxed at 65° C. for 2 h. The solution was allowed to cool to ambient temperature. The aqueous layer was washed with dichloromethane (20 mL). The aqueous solution was transferred to an Erlenmeyer flask and acidified to pH˜1 with conc. HCl. This solution was then extracted with EtOAc (3×20 mL) and the combined organic layers were dried over Na2SO4, filtered and evaporated. The residue was purified on silica gel (flash column chromatography) eluting with 5% ethyl acetate-hexane followed by 20% ethyl acetate-hexane to provide the desired product as white solid. The desired product was white solid (0.33 g, 16.5% ). 1H-NMR (CD3CN) δ 7.93 (broad s, 1H, OH), 7.26 (s, 1H), 6.28 (s, 1H), 2.69 (t, 2H), 1.80 (t, 2H), 1.32 (s, 6H). In a 250 mL round-bottom flask was placed was added dropwise The reaction mixture was cooled down to 0° C. The solution was then refluxed at 65° C. for 2 h to cool to ambient temperature The aqueous layer was washed with dichloromethane (20 mL) This solution was then extracted with EtOAc (3×20 mL) the combined organic layers were dried over Na2SO4 filtered evaporated The residue was purified on silica gel (flash column chromatography) eluting with 5% ethyl acetate-hexane

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a stirred solution of 7-Methoxy-2,2-dimethyl-chroman (4.55 g, 23.7 mmol, from step 1) in anhydrous dichloromethane (50 mL) was added 1M BBr3 (72.86 mL, 47.4 mmol, 2.0 eq ) via cannula over 10 min. The resulting dark brown solution was stirred at rt for 17 h. Saturated solution of NaHCO3 (50 mL) was added and extracted with CH2Cl2 (3×50 mL. The combined organic layers were dried over Na2SO4, filtered and evaporated. The residue was purified on silica gel (flash column chromatography) eluting with 5% ethyl acetate-hexane followed by 20% ethyl acetate-hexane to provide the desired product as white solid (1.76 g, 42%). 1H-NMR (CD3CN) δ 6.89 (d, J=8.5 Hz, 1H), 6.68 (broad, s, 1H, OH), 6.31 (dd, J=2.4, 8.5 Hz, 1H), 6.15 (d, J=2.4Hz, 1H ), 2.69 (t, 2H ), 1.79 (t, 2H), 1.31 (s, 6H). MS LC-MS (MH+=179). extracted with CH2Cl2 (3×50 mL The combined organic layers were dried over Na2SO4 filtered evaporated The residue was purified on silica gel (flash column chromatography) eluting with 5% ethyl acetate-hexane