methyl 3-bromo-2-(bromomethyl)benzoate

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

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: Methyl 3-bromo-2-(bromomethyl)benzoate (1.28 g) was dissolved in a 11% solution of ammonia in methanol-THF mixed solution (3:2, 25 ml) and the mixture was stirred at room temperature for 16 h. The reaction mixture was concentrated and the residue was washed with saturated brine. Recrystallization from ethyl acetate-hexane gave the title compound (671 mg, 76%) as colorless needle crystals. The reaction mixture was concentrated the residue was washed with saturated brine Recrystallization from ethyl acetate-hexane

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

実験手順: Methyl 3-bromo-2-(bromomethyl)benzoate (1.28 g) was dissolved in a 11% solution of ammonia in methanol-THF mixed solution (3:2, 25 ml) and the mixture was stirred at room temperature for 16 h. The reaction mixture was concentrated and the residue was washed with saturated brine. Recrystallization from ethyl acetate-hexane gave the title compound (671 mg, 76%) as colorless needle crystals. The reaction mixture was concentrated the residue was washed with saturated brine Recrystallization from ethyl acetate-hexane

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

実験手順: A solution of methyl 3-bromo-2-methylbenzoate (1.00 g), N-bromosuccinimide (855 mg) and 2,2′-azobis(isobutyronitrile) (71.8 mg) in carbon tetrachloride (50 ml) was heated under reflux for 8 h. The reaction mixture was concentrated, and the residue was diluted with ethyl acetate, washed with saturated aqueous sodium hydrogen carbonate and saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by column chomatography (eluent; hexane:ethyl acetate=20:1) to give the title compound (1.29 g) as a colorless oil. under reflux for 8 h The reaction mixture was concentrated the residue was diluted with ethyl acetate washed with saturated aqueous sodium hydrogen carbonate and saturated brine dried over anhydrous magnesium sulfate The solvent was evaporated under reduced pressure the residue was purified by column chomatography (eluent; hexane:ethyl acetate=20:1)

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

実験手順: The procedure of the step 2 in Example 1 was repeated except that methyl 3-bromo-2-(bromomethyl)benzoate instead of methyl 3-bromo-2-(bromomethyl)-4,5-dimethoxybenzoate, methyl 6-aminohexanoate hydrochloride instead of methyl 4-(aminomethyl)benzoate hydrochloride, triethylamine (2.4 equiv.), and THF as a solvent were used and the reaction was conducted for 20 hrs, to obtain the title compound (99%).

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

実験手順: To a flask containing methyl 2-((tert-butoxycarbonyl)amino)acetate (4.18 g, 22.09 mmol) in anhydrous DMF (50 ml) was added KOtBu (3.99 g, 35.6 mmol) then after 1 min at room temperature added methyl 3-bromo-2-(bromomethyl)benzoate (4.97 g, 16.14 mmol) as a solid in 1 portion. The reaction mixture was then capped (not under N2) & stirred at room temperature for 3 hours. Followed by LC/MS. The reaction mixture was quenched/diluted with sat'd NaHCO3, then suspended in EtOAc, washed with saturated NaHCO3, then H2O, then brine; organics dried over Na2SO4, filtered & concentrated. Purification by silica gel chromatography (0-20% EtOAc/Hex; 220 g ISCO); desired fractions concentrated to yield 2-tert-butyl 3-methyl 8-bromo-4-oxo-3,4-dihydroisoquinoline-2,3 (1H)-dicarboxylate (24-1). The reaction mixture was then capped (not under N2) & washed with saturated NaHCO3 organics dried over Na2SO4 filtered concentrated Purification by silica gel chromatography (0-20% EtOAc/Hex; 220 g ISCO) desired fractions concentrated

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

実験手順: Methyl 3-bromo-2-methylbenzoate (7.45 g, 32.5 mmol) was dissolved in CCl4 (94 ml) and N-bromosuccinimide (6.67 g, 37.5 mmol) and benzoyl peroxide (0.38 g, 1.6 mmol) were added. The reaction was heated to 75 C-85 C, stirred for 3 hours and 45 minutes, cooled to room temperature, and filtered. The filtrate was concentrated and purified on SiO2 (Biotage instrument; 0%->20% EtOAc/hexanes) to give methyl 3-bromo-2-(bromomethyl)benzoate (10.07 g, 100%). The reaction was heated to 75 C-85 C filtered The filtrate was concentrated purified on SiO2 (Biotage instrument; 0%->20% EtOAc/hexanes)

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

実験手順: Triethylamine (4.66 g, 46.09 mmol) was added to a stirred suspension of methyl 3-bromo-2-bromomethylbenzoate (6.45 g, 20.95 mmol) and L-glutamine t-butyl ester hydrochloride (5.0 g, 20.95 mmol) in THF (100 mL). The mixture was heated to reflux for 18 hours. The mixture was cooled to room temperature and solvent was removed. The residue was dissolved in methylene chloride (100 mL) and washed with water (2×80 mL), brine (80 mL) and dried (MgSO4). Solvent was removed and the residue was purified by chromatography (CH2Cl2: CH3OH 97.5:2.5) to afford tert-butyl 2-(4-bromo-1-oxoisoindolin-2-yl)-4-carbamoylbutanoate 3.97 g, 48%): 1H NMR (CDCl3) δ 7.74 (d, J=7.1 Hz, 1H), 7.65 (d, J=7.9 Hz, 1H), 7.35 (t, J=7.8 Hz, 1H), 6.15 (s, 1H), 5.77 (s, 1H), 5.02-4.96 (m, 1H), 4.58 (d, J=17.4 Hz, 1H), 4.34 (d, J=17.4 Hz, 1H), 2.45-2.10 (m, 4H), 1.46 (s, 9H); 13C NMR (CDCl3) δ 173.83, 169.42, 168.74, 142.28, 134.70, 133.65, 129.80, 122.70, 117.75, 82.66, 54.29, 47.80, 32.27, 27.95, 25.54. The mixture was heated to reflux for 18 hours solvent was removed The residue was dissolved in methylene chloride (100 mL) washed with water (2×80 mL), brine (80 mL) dried (MgSO4) Solvent was removed the residue was purified by chromatography (CH2Cl2: CH3OH 97.5:2.5)

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

実験手順: A mixture of methyl 3-bromo-2-methylbenzoate (17.0 g, 74.22 mmol) and N-bromosuccinimide (15.85 g, 89.06 mmol) in acetonitrile (200 mL) was heated under gently refluxing for 17 hours while a 200 W bulb situated 2 cm away was shining on the reaction flask. The mixture was cooled to room temperature and solvent was removed. The residue was dissolved in ethyl acetate (200 mL) and washed with water (3×80 mL), brine (80 mL) and dried (MgSO4). Solvent was removed to give methyl 3-bromo-2-bromomethylbenzoate (24.5 g, 97% by HPLC): 1H NMR (CDCl3) δ 7.90-7.86 (dd, J=1.0 and 7.9 Hz, 1H), 7.78-7.74 (dd, J=1.2 and 8.2 Hz, 1H), 7.22 (t, J=7.9 Hz, 1H), 5.12 (s, 2H), 3.95 (s, 3H). was heated under gently refluxing for 17 hours while a 200 W bulb solvent was removed The residue was dissolved in ethyl acetate (200 mL) washed with water (3×80 mL), brine (80 mL) dried (MgSO4) Solvent was removed