6-bromo-2,3-dihydrochromen-4-one

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: The starting material 6-bromochroman-3-one (5A) was prepared from 6-bromochroman-4-one in a manner similar to that described in the literature (Synthesis, 1980, 621): 6-bromochroman-4-one was reduced with NaBH4 (1.2 eq, MeOH-DCM, 0° C. to RT, 2h) and then eliminated with pTsOH (cat., toluene, reflux, 3h, 90% for 2-steps). The resulting 6-bromochromene was subjected to osmylation (cat. OsO4, 1 eq. NMO, water-acetone-tBuOH, RT, overnight) and subsequent treatment with pTsOH (cat., toluene, reflux, 15 min, 86% for 2-steps) to provide 6-bromochroman-3-one (5A). that described in the literature (Synthesis, 1980, 621)

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Following the procedure of Example 1, para-bromophenol (43.25 grams), acrylic acid (27 grams) and phenothiazine (0.02 grams) were added to the pressure reactor. The system was closed and evacuated before being cooled to -78° C. and the anhydrous hydrogen fluoride (110 grams) was added. After the mixture was heated and stirred for six hours at 100° C., 140 psig, the excess hydrogen fluoride was vented and the reaction mixture cooled to 0°-5° C. After washing the mixture with D.I. water, HPLC analysis indicated one major product which was separated and characterized as 6-Bromo-4-Chromanone. were added to the pressure reactor The system was closed evacuated the anhydrous hydrogen fluoride (110 grams) was added After the mixture was heated the reaction mixture cooled to 0°-5° C After washing the mixture with D.I was separated

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-2,3-dihydro-4H-chromen-4-one (0.3 g, 1.3 mmol), paraformaldehyde (0.48 g), L-proline (61 mg, 0.53 mmol), and 0.2 M aqueous sodium hydroxide (6 mL) was stirred at room temperature for 16 hours. The mixture was extracted with CHCl3 and concentrated in vacuo. The residue was purified with silica-gel column chromatography (CHCl3/MeOH=100:0 to 90:10) to give 6-bromo-3,3-bis(hydroxymethyl)-2,3-dihydro-4H-chromen-4-one (0.33 g). The mixture was extracted with CHCl3 concentrated in vacuo The residue was purified with silica-gel column chromatography (CHCl3/MeOH=100:0 to 90:10)

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-2,3-dihydro-4H-chromen-4-one (0.3 g, 1.3 mmol), paraformaldehyde (0.48 g), L-proline (61 mg, 0.53 mmol), and 0.2 M aqueous sodium hydroxide (6 mL) was stirred at room temperature for 16 hours. The mixture was extracted with CHCl3 and concentrated in vacuo. The residue was purified with silica-gel column chromatography (CHCl3/MeOH=100:0 to 90:10) to give 6-bromo-3,3-bis(hydroxymethyl)-2,3-dihydro-4H-chromen-4-one (0.33 g). The mixture was extracted with CHCl3 concentrated in vacuo The residue was purified with silica-gel column chromatography (CHCl3/MeOH=100:0 to 90:10)

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-2,3-dihydro-4H-chromen-4-one (0.3 g, 1.3 mmol), paraformaldehyde (0.48 g), L-proline (61 mg, 0.53 mmol), and 0.2 M aqueous sodium hydroxide (6 mL) was stirred at room temperature for 16 hours. The mixture was extracted with CHCl3 and concentrated in vacuo. The residue was purified with silica-gel column chromatography (CHCl3/MeOH=100:0 to 90:10) to give 6-bromo-3,3-bis(hydroxymethyl)-2,3-dihydro-4H-chromen-4-one (0.33 g). The mixture was extracted with CHCl3 concentrated in vacuo The residue was purified with silica-gel column chromatography (CHCl3/MeOH=100:0 to 90:10)

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-2,3-dihydro-4H-chromen-4-one (0.3 g, 1.3 mmol), paraformaldehyde (0.48 g), L-proline (61 mg, 0.53 mmol), and 0.2 M aqueous sodium hydroxide (6 mL) was stirred at room temperature for 16 hours. The mixture was extracted with CHCl3 and concentrated in vacuo. The residue was purified with silica-gel column chromatography (CHCl3/MeOH=100:0 to 90:10) to give 6-bromo-3,3-bis(hydroxymethyl)-2,3-dihydro-4H-chromen-4-one (0.33 g). The mixture was extracted with CHCl3 concentrated in vacuo The residue was purified with silica-gel column chromatography (CHCl3/MeOH=100:0 to 90:10)

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 6-Bromochroman-4-one (5.0 g, 22 mmol) and 2-methylpropane-2-sulfinamide (2.6 g, 22 mmol) were dissolved in dry THF (80 mL). Titanium ethoxide (10 g, 44 mmol) was added. The resulting mixture was heated at 60° C. for 2 days. An additional portion of titanium ethoxide (1.0 g, 8.4 mmol) was added after 12 h. The mixture was mixed with heptane and evaporated onto silica gel. Flash chromatography on silica (0-50% EtOAc in heptane) gave the title compound (6.0 g, 83% yield). 1H NMR (500 MHz, CDCl3) δ ppm 1.34 (s, 9 H) 3.26-3.32 (m, 1 H) 3.47-3.54 (m, 1 H) 4.28-4.40 (m, 2 H) 6.83 (d, 1 H) 7.46 (dd, 1 H) 8.06 (d, 1 H); MS (ES+) m/z 330 [M+H]+. evaporated onto silica gel

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 6-Bromochroman-4-one (5.0 g, 22 mmol) and 2-methylpropane-2-sulfinamide (2.6 g, 22 mmol) were dissolved in dry THF (80 mL). Titanium ethoxide (10 g, 44 mmol) was added. The resulting mixture was heated at 60° C. for 2 days. An additional portion of titanium ethoxide (1.0 g, 8.4 mmol) was added after 12 h. The mixture was mixed with heptane and evaporated onto silica gel. Flash chromatography on silica (0-50% EtOAc in heptane) gave the title compound (6.0 g, 83% yield). 1H NMR (500 MHz, CDCl3) δ ppm 1.34 (s, 9 H) 3.26-3.32 (m, 1 H) 3.47-3.54 (m, 1 H) 4.28-4.40 (m, 2 H) 6.83 (d, 1 H) 7.46 (dd, 1 H) 8.06 (d, 1 H); MS (ES+) m/z 330 [M+H]+. evaporated onto silica gel

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

実験手順: 4-Bromophenol (105 g, 0.61 mole) was converted into methyl(4-bromophenoxy)propanoate by the method referred to in Description 11A. This ester (125 g, 0.48 mole) was then added slowly to concentrated sulphuric acid (500 ml) and the resulting yellow solution stirred at room temperature for 30 minutes. This solution was poured slowly into ice/water (5 liters) and the mixture extracted using ethyl acetate (2×700 ml). The organic solution was washed with 10% sodium carbonate solution (2×300 ml) and brine (1×300 ml), dried (Na2SO4) and evaporated to dryness to give a pale yellow solid. This was recrystallised from ethyl acetate/petroleum ether (60°-80° C.) to give the title compound as a white crystalline solid (43.4 g, 31%). M.p. 79°-80°. the mixture extracted The organic solution was washed with 10% sodium carbonate solution (2×300 ml) and brine (1×300 ml) dried (Na2SO4) evaporated to dryness to give a pale yellow solid This was recrystallised from ethyl acetate/petroleum ether (60°-80° C.)

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

実験手順: The title compound was prepared by the method of Canalini et al.2 by the reaction of 4-bromophenol (40 g, 0.23 mole) and methyl acrylate (100 ml) in the presence of Triton B (6 ml of a 40% solution in methanol); followed by dilute acid hydrolysis of the resulting ester and cyclisation of the (4-bromophenoxy)propionic acid in concentrated sulphuric acid. The product was recrystallised from petroleum ether (60°-80° C.) to give a white crystalline solid (6.80 g, 13%). M.p. 78°-80° C. by dilute The product was recrystallised from petroleum ether (60°-80° C.)

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

実験手順: The title compound was prepared by the method of Canalini et al.2 by the reaction of 4-bromophenol (40 g, 0.23 mole) and methyl acrylate (100 ml) in the presence of Triton B (6 ml of a 40% solution in methanol); followed by dilute acid hydrolysis of the resulting ester and cyclisation of the (4-bromophenoxy)propionic acid in concentrated sulphuric acid. The product was recrystallised from petroleum ether (60°-80° C.) to give a white crystalline solid (6.80 g, 13%). M.p. 78°-80° C. by dilute The product was recrystallised from petroleum ether (60°-80° C.)