4-bromo-3-methoxyphenol

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Following the procedure as described in PREPARATION 1C, and making non-critical variations to replace 4-bromo-1-pentyl-1H-indole-2,3-dione with 1-pentyl-1H-indole-2,3-dione, and 1,3-benzodioxol-5-ol with 4-bromo-3-methoxyphenol, the title compound was obtained (48%): 1H NMR (300 MHz, CDCl3) δ 9.85 (s, 1H), 7.52-7.38 (m, 2H), 7.22 (td, 1H), 6.94 (d, 1H), 6.89 (s, 1H), 6.63 (s, 1H), 4.13-4.03 (br, 1H)3.86(s, 3H), 3.80-3.57 (m, 2H), 1.75-1.63 (m, 2H), 1.40-1.25 (m, 4H), 0.88 (t, 3H); MS (ES+) m/z 402 (M−17), 404 (M−17), 442 (M+23), 444 (M+23).

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1.50 g (7.39 mmol) 4-bromo-3-methoxy-phenol are added to 1.36 g (11.1 mmol) 1-bromopropane in 10 mL DMF. 2.04 g (14.8 mmol) K2CO3 are added and the mixture is stirred at 80° C. for 12 h. After that time, the mixture is diluted with water and extracted with DCM. The organic layer is dried over sodium sulphate and the solvent is removed in vacuo. extracted with DCM The organic layer is dried over sodium sulphate the solvent is removed in vacuo

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 4-bromo-3-methoxyphenol (500 mg, 2.46 mmol), chlorodimethylether (281 μL, 3.70 mmol), and potassium carbonate (850 mg, 6.15 mmol) was suspended in anhydrous N,N-dimethylformamide (8 mL) and stirred at 50° C. for 1 hour. After cooling down, the reaction mixture was diluted with ethyl acetate (150 mL). The mixture was washed with water (150 mL) and saturated brine (50 mL) successively, dried over anhydrous magnesium sulfate, and then the solvent was removed under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane-ethyl acetate) to give the titled reference compound (421 mg) as a colorless oil. (Yield 69%) After cooling down The mixture was washed with water (150 mL) and saturated brine (50 mL) successively dried over anhydrous magnesium sulfate the solvent was removed under reduced pressure The obtained residue was purified by silica gel column chromatography (hexane-ethyl acetate)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a 5 L round bottom flask fitted with an overhead stirrer, thermocouple and N2 inlet, was added 4-bromo-3-methoxyphenol (254 g, 1251 mmol), DCM (2500 mL) and DIPEA (437 mL, 2502 mmol). The reaction mixture was cooled in an ice bath, followed by addition of tert-butylchlorodimethylsilane (198 g, 1314 mmol). The reaction mixture was stirred at RT overnight, and then diluted with water. The organic layer was separated, dried over sodium sulfate, filtered and concentrated to provide (4-bromo-3-methoxyphenoxy)(tert-butyl)dimethylsilane (472 g, 1250 mmol, 100% yield). MS (M+1)=319.2. To a 5 L round bottom flask fitted with an overhead stirrer The reaction mixture was cooled in an ice bath The organic layer was separated dried over sodium sulfate filtered concentrated

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 4-bromo-3-methoxyphenol (500 mg, 2.46 mmol), chlorodimethylether (281 μL, 3.70 mmol), and potassium carbonate (850 mg, 6.15 mmol) was suspended in anhydrous N,N-dimethylformamide (8 mL) and stirred at 50° C. for 1 hour. After cooling down, the reaction mixture was diluted with ethyl acetate (150 mL). The mixture was washed with water (150 mL) and saturated brine (50 mL) successively, dried over anhydrous magnesium sulfate, and then the solvent was removed under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane-ethyl acetate) to give the titled reference compound (421 mg) as a colorless oil. (Yield 69%) After cooling down The mixture was washed with water (150 mL) and saturated brine (50 mL) successively dried over anhydrous magnesium sulfate the solvent was removed under reduced pressure The obtained residue was purified by silica gel column chromatography (hexane-ethyl acetate)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Following the procedure as described in PREPARATION 1C, and making non-critical variations to replace 4-bromo-1-pentyl-1H-indole-2,3-dione with 1-pentyl-1H-indole-2,3-dione, and 1,3-benzodioxol-5-ol with 4-bromo-3-methoxyphenol, the title compound was obtained (48%): 1H NMR (300 MHz, CDCl3) δ 9.85 (s, 1H), 7.52-7.38 (m, 2H), 7.22 (td, 1H), 6.94 (d, 1H), 6.89 (s, 1H), 6.63 (s, 1H), 4.13-4.03 (br, 1H), 3.86 (s, 3H), 3.80-3.57 (m, 2H), 1.75-1.63 (m, 2H), 1.40-1.25 (m, 4H), 0.88 (t, 3H); MS (ES+) m/z 402 (M−17), 404 (M−17), 442 (M+23), 444 (M+23).

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred mixture of K2CO3 (3.45 g, 0.025 mol), and 3-methoxy-4-bromo-phenol (6.09 g, 0.030 mol) at ambient temperature under argon is added allyl bromide (3.60 g, 0.030 mol). The resulting mixture is heated and stirred overnight. The mixture is filtered and the filtrate is concentrated on the rotovap. The residue is partitioned between Et2O and H2O. The Et2O layer is separated and extracted with 2×70 ml 5% NaOH, washed with brine, dried (MgSO4) and filtered. Evaporation on the rotovap followed by flash chromatography (EtOAc-hexane 1:9) gives 5.93 (81%) of the title compound. Rf-0.41 (EtOAc-hexane 25:75) HNMR (CDCl3) d 7.38 (d, 1H), 6.38 (dd, 1H) 6.1-5.9 (m, 1H), 5.41 (d, 1H), 5.29 (d, 1H), 4.51-4.48 (m, 2H), 3.84 (s, 3H). The resulting mixture is heated The mixture is filtered the filtrate is concentrated on the rotovap The residue is partitioned between Et2O and H2O The Et2O layer is separated extracted with 2×70 ml 5% NaOH washed with brine dried (MgSO4) filtered Evaporation on the rotovap

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred suspension of 4-bromo-3-methoxyphenol (2.03 g, 10 mmol) and K2CO3 (1.38 g, 10 mmol) in 2-butanone (70 mL) at ambient temperature under argon is added dropwise isopropyl iodide (2.21 g, 13.3 mmol). The resulting mixture is heated and stirred under reflux for 17 hours. The mixture is allowed to cool to ambient temperature then is filtered and concentrated by evaporation of the solvent. The residue is partitioned between Et2O and H2O. The Et2O layer is extracted with 5% NaOH (2×50 mL), washed with brine, and dried over MgSO4. The solvent is evaporated and the resulting residue is purified by flash chromatography (5% EtOAc/hexane) to afford the desired compound as a pale yellow oil. 2.13 g (87%). The resulting mixture is heated under reflux for 17 hours then is filtered concentrated by evaporation of the solvent The residue is partitioned between Et2O and H2O The Et2O layer is extracted with 5% NaOH (2×50 mL) washed with brine dried over MgSO4 The solvent is evaporated the resulting residue is purified by flash chromatography (5% EtOAc/hexane)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Prepare a solution of 4-bromo-3-methoxyphenol (6.5 g, 32 mmole), and potassium carbonate (15 g) in acetone (250 mL) under argon. Add n-propyl iodide (9.0 g, 5.2 mL, 53 mmole) and heat to reflux overnight. Cool to room temperature and filter. Rotovap to condense and evaporate the solvents. Check by thin layer chromatagraphy (25% ethyl aceate/75% hexane). Wash three times with 100 mL 3% potassium hydroxide. Dry the organic layer with magnesium sulfate. Filter and rotovap. Purify by chromatography and place under high vacuum to obtain the title compound (6.9 g, 88%). Rf=0.60 (EtOAc/hexane; 25:75). to reflux overnight filter Rotovap to condense evaporate the solvents Wash three times with 100 mL 3% potassium hydroxide Dry the organic layer with magnesium sulfate Filter Purify by chromatography and place under high vacuum

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3-Methoxy-4-bromophenol D8 (6.95 g, 34 mmoles) in dry dimethylformamide (100 ml) at 0° C. was treated with sodium hydride (80% dispersion in oil) (1.13 g, 37 mmoles). After 30 mins ethyl bromoacetate (3.8 ml, 34 mmoles) was added and the mixture allowed to warm to room temperature over 1 hr. The mixture was concentrated in vacuo and the residue partitioned between water and diethyl ether. The organic layer was washed several times with water and then dried (Na2SO4) and evaporated to dryness. Flash chromatography on TLC silica gel eluting with dichloromethane gave the title compound (D9) (7.43 g, 75%) The mixture was concentrated in vacuo the residue partitioned between water and diethyl ether The organic layer was washed several times with water dried (Na2SO4) evaporated to dryness