4-bromo-2-chlorophenol

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

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

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

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

Conditions: temp:80.01; 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: Synthesised by analogous methods to Intermediate 2b, using 4-bromo-2-chloro-phenol at Stage 6 of Scheme 2. m/z 524 [M+H]+.

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A dry 250 ml r.b. flask was loaded with 4-bromo-2-chlorophenol (5.00 g, 24.1 mmol) and purged with N2 (g). Anhydrous THF (100 mL) added with stirring and the vessel cooled to −78° C. (dry ice/acetone bath). After 30 mins n-BuLi, 2.3 M in hexanes, (12.9 mL, 28.9 mmol) was added dropwise over 20 min. The reaction was left to stir for 1 h. Triisopropyl borate (6.65 mL, 28.9 mmol) was added dropwise with the reaction still at −78° C. After 15 min of stirring at this temperature the dry ice/acetone bath was removed. At about 0° C. 2 M HCl(aq) (5 mL) was added and the reaction left to stir for a further 15 min. THF removed under vacuum and residues taken up in ethyl acetate (50 mL). Distilled H2O (50 mL) was added and the organic layer separated. The aqueous layer was extracted with ethyl acetate (50 mL×2). The organic portions were combined and washed with sat. Na2CO3 (aq). The aqueous layer was separated and treated with 2M HCl (aq) until the pH was about 4. This was then extracted with ethyl acetate (50 mL×2). The organic portions were then dried over MgSO4 and solvent removed. The resultant off white residues were taken up in a minimum of ethyl acetate (2-3 mL) and added to dropwise to hexane (50 mL) with stirring. The white ppt was filtered to give the title compound as an off white solid (0.490 g, 12%). purged with N2 (g) Anhydrous THF (100 mL) added The reaction was left to stir for 1 h was removed At about 0° C 2 M HCl(aq) (5 mL) was added the reaction left to stir for a further 15 min THF removed under vacuum and residues Distilled H2O (50 mL) was added the organic layer separated The aqueous layer was extracted with ethyl acetate (50 mL×2) washed with sat. Na2CO3 (aq) The aqueous layer was separated treated with 2M HCl (aq) until the pH was about 4 This was then extracted with ethyl acetate (50 mL×2) The organic portions were then dried over MgSO4 and solvent removed added to dropwise to hexane (50 mL) with stirring The white ppt was filtered

Conditions: temp:85.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of 4-bromo-2-chlorophenol (1.00 g, 4.82 mmol) and cesium carbonate (3.14 g, 9.64 mmol) in DMF (6.89 mL) at room temperature was added 4-bromo-2-methyl-2-butene (0.68 mL, 5.78 mmol) dropwise via a syringe. The reaction mixture was stirred at 85° C. for 1 hour before it was allowed to cool to room temperature. Water (30.0 mL) was then added and the mixture was extracted with hexane (75.0 mL, 2×). The combined organic layers were dried over Na2SO4, filtered and concentrated under vacuum. The crude mixture was purified by silica gel chromatography eluting with 0-5% EtOAc/hexanes to afford the product as a colorless oil. to cool to room temperature the mixture was extracted with hexane (75.0 mL, 2×) The combined organic layers were dried over Na2SO4 filtered concentrated under vacuum The crude mixture was purified by silica gel chromatography eluting with 0-5% EtOAc/hexanes

Conditions: temp:85.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of 4-bromo-2-chlorophenol (0.98 g, 4.71 mmol), and Cs2CO3 (2.05 g, 6.28 mmol) in DMF (4.49 mL) at room temperature was added 3-methylbut-3-en-1-yl diphenyl phosphate (1.00 g, 3.14 mmol, synthesized according to a procedure in U.S. Pat. No. 5,006,550, 9 Apr. 1991) dropwise via a syringe. The reaction mixture was heated to 85° C. for 1 hour. It was then allowed to cool to room temperature and was diluted with water (20.0 mL). The resulting mixture was extracted with hexane (75.0 mL, 2×) and the combined organic layers were dried over Na2SO4, filtered, and concentrated under vacuum. The crude mixture was purified by silica gel chromatography eluting with 0-5% EtOAc/hexanes to give the title compound as a colorless oil. synthesized to cool to room temperature The resulting mixture was extracted with hexane (75.0 mL, 2×) the combined organic layers were dried over Na2SO4 filtered concentrated under vacuum The crude mixture was purified by silica gel chromatography eluting with 0-5% EtOAc/hexanes

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

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