2-氯-4-溴苯甲醇

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:

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: To a stirred solution of (4-bromo-2-chlorophenyl)methanol (4.34 g, 19.6 mmol) in dichloromethane (98 mL) at 0° C. is added carbon tetrabromide (6.5 g, 19.6 mmol) and triphenylphosphine (5.14 g, 19.6 mmol). The reaction mixture is stirred 16 h at room temperature. Then, the solvent is removed and the crude solid suspended in hexanes/EtOAc 9:1 (100 mL) and filtered on a silica gel pad. The pad is rinsed with hexanes/EtOAc 9:1 (100 mL) and the filtrate is concentrated in vacuo to provide the expected product 4-bromo-1-(bromomethyl)-2-chlorobenzene (7.19 g, 129%) contaminated with bromoform. 1H NMR (300 MHz, CHLOROFORM-D): δ 7.57 (1H, d, J=2.0 Hz), 7.39 (1H, dd, J=8.2, 2.0 Hz), 7.30 (1H, d, J=8.2 Hz), 4.53 (2H, s). Then, the solvent is removed filtered on a silica gel pad The pad is rinsed with hexanes/EtOAc 9:1 (100 mL) the filtrate is concentrated in vacuo

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 4-bromo-2-chlorobenzoic acid (4.27 g, 18.1 mmol) in tetrahydrofuran (39 mL) at 0° C. is added borane-tetrahydrofuran complex (1 M in THF) (36.3 mL, 36.3 mmol). The reaction mixture is stirred 16 h at room temperature. At 0° C., water is slowly added then NaHCO3 aq. sat. is also slowly added The resulting solution is extracted with EtOAc (3×50 mL). The combined organic layer is washed with brine, dried over anhydrous MgSO4, filtered and concentrated under reduced pressure. The crude product is purified by flashchromatography (eluent: Hexanes/EtOAc 85:15 to 70:30) to provide the expected product (4-bromo-2-chlorophenyl)methanol (4.34 g, 108%). 1H NMR (300 MHz, CHLOROFORM-D): δ 7.53 (1H, d, J=1.8 Hz), 7.43 (1H, dd, J=8.2, 1.8 Hz), 7.38 (1H, d, J=8.2 Hz), 4.74 (2H, d, J=6.2 Hz), 1.90 (1H, t, J=6.3 Hz). is extracted with EtOAc (3×50 mL) The combined organic layer is washed with brine dried over anhydrous MgSO4 filtered concentrated under reduced pressure The crude product is purified by flashchromatography (eluent: Hexanes/EtOAc 85:15 to 70:30)

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Phosphorus tribromide (40.5 mL, 0.431 mol) was added dropwise to a solution of (4-bromo-2-chlorophenyl)-methanol (15, 86.1 g, 0.386 mol) in dichloroethane (430 mL) at 0° C. The reaction mixture was stirred for 10 minutes at this temperature then for 0.5 h at 10° C. The mixture was cooled to 0° C. and a sodium hydroxide solution (600 mL, 2N) was added dropwise. The two layers were separated and the aqueous layer was extracted with dichloroethane (200 mL). The combined organic layers were washed with water (200 mL), dried over sodium sulfate and evaporated in vacuo. The crude product (91 g) was distilled under reduced pressure (7 mmHg), to give 4-bromo-1-bromomethyl-2-chlorobenzene (62.5 g, 0.22 mol, 57%) as a colorless oil. for 0.5 h at 10° C The two layers were separated the aqueous layer was extracted with dichloroethane (200 mL) The combined organic layers were washed with water (200 mL) dried over sodium sulfate evaporated in vacuo The crude product (91 g) was distilled under reduced pressure (7 mmHg)

反应条件: temp:-15.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 4-Bromo-2-chlorobenzoic acid (14, 92.0 g, 0.39 mol) was dissolved in dry tetrahydrofuran (920 mL) and cooled to −15° C. Isobutyryl choroformate (51.0 mL, 0.39 mol) was added followed by N-methylmorpholine (43.5 mL, 0.39 mol). The resulting mixture was stirred for 10 minutes at −15° C., cooled to −25° C. and the precipitated N-methylmorpholine hydrochloride salt was filtered off. The filtrate was warmed to −5° C. and a solution of sodium borohydride (22.19 g, 0.586 mol) in water (190 mL) was added dropwise to the mixture keeping the temperature below 0° C. After stirring for 1 h at 0° C., the volatiles were evaporated, and the residue was diluted with water (500 mL) and dichloromethane (450 mL). The layers were separated and the aqueous layer was extracted with dichloromethane (150 mL). The combined organic layers were washed with water (150 mL), dried over sodium sulfate and evaporated. The product (86.1 g, 0.39 mol, 99%) was obtained as a white crystalline solid. cooled to −25° C. the precipitated N-methylmorpholine hydrochloride salt was filtered off The filtrate was warmed to −5° C. the temperature below 0° C After stirring for 1 h at 0° C. the volatiles were evaporated the residue was diluted with water (500 mL) and dichloromethane (450 mL) The layers were separated the aqueous layer was extracted with dichloromethane (150 mL) The combined organic layers were washed with water (150 mL) dried over sodium sulfate evaporated

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

实验步骤: To a solution of 4-bromo-2-chlorobenzyl alcohol (14.48 g) in N,N-dimethylformamide (72 ml) were added imidazole (5.34 g) and tert-butylchlorodiphenylsilane (19.8 g) under ice-cooling and the mixture was stirred for 1 hr. Water was added to the reaction mixture and the resulting product was extracted twice with hexane. The organic layers were combined, and washed successively with water, a saturated aqueous solution of sodium hydrogen-carbonate and saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated and the residue was subjected to silica gel column chromatography (hexane) to give the objective compound (29.22 g) as colorless oil. cooling the resulting product was extracted twice with hexane washed successively with water a saturated aqueous solution of sodium hydrogen-carbonate and saturated brine and dried over anhydrous magnesium sulfate The solvent was evaporated

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

实验步骤: To a solution of 4-bromo-2-chlorobenzyl alcohol (14.48 g) in N,N-dimethylformamide (72 ml) were added imidazole (5.34 g) and tert-butylchlorodiphenylsilane (19.8 g) under ice-cooling and the mixture was stirred for 1 hr. Water was added to the reaction mixture and the resulting product was extracted twice with hexane. The organic layers were combined, and washed successively with water, a saturated aqueous solution of sodium hydrogen-carbonate and saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated and the residue was subjected to silica gel column chromatography (hexane) to give the objective compound (29.22 g) as colorless oil. cooling the resulting product was extracted twice with hexane washed successively with water a saturated aqueous solution of sodium hydrogen-carbonate and saturated brine and dried over anhydrous magnesium sulfate The solvent was evaporated