3-BROMOPHENETOLE

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

Procedure: Acetic anhydride (1.25 mL, 12.2 mmol) was added to a solution of 5-amino-2-methyl phenol (1.0 g, 8.1 mmol) in acetic acid (6 mL), and the reaction was refluxed for 5 mins. Then the reaction mixture was cooled to room temperature and the product was solidified. It was filtered off and washed with water (4 mL) and dried to obtain the product along with the trace amount of O-acylated product. The mixture, to which was added 3-bromophenetole (1.33 g, 6.6 mmol) and Cs2CO3 (2.927 g, 9.0 mmol) in DMF (10 mL), was stirred overnight at 50° C. The reaction mixture was then diluted with water (10 mL) and extracted with ethyl acetate (3×20 mL). The combined extracts were dried over sodium sulfate and recrystallized from toluene to obtain the pure product 18a in 65% (yield over two steps) as an off-white solid. the reaction was refluxed for 5 mins It was filtered off washed with water (4 mL) dried to obtain the product along with the trace amount of O-acylated product extracted with ethyl acetate (3×20 mL) The combined extracts were dried over sodium sulfate recrystallized from toluene

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

Procedure: Acetic anhydride (1.25 mL, 12.2 mmol) was added to a solution of 5-amino-2-methyl phenol (1.0 g, 8.1 mmol) in acetic acid (6 mL), and the reaction was refluxed for 5 mins. Then the reaction mixture was cooled to room temperature and the product was solidified. It was filtered off and washed with water (4 mL) and dried to obtain the product along with the trace amount of O-acylated product. The mixture, to which was added 3-bromophenetole (1.33 g, 6.6 mmol) and Cs2CO3 (2.927 g, 9.0 mmol) in DMF (10 mL), was stirred overnight at 50° C. The reaction mixture was then diluted with water (10 mL) and extracted with ethyl acetate (3×20 mL). The combined extracts were dried over sodium sulfate and recrystallized from toluene to obtain the pure product 18a in 65% (yield over two steps) as an off-white solid. the reaction was refluxed for 5 mins It was filtered off washed with water (4 mL) dried to obtain the product along with the trace amount of O-acylated product extracted with ethyl acetate (3×20 mL) The combined extracts were dried over sodium sulfate recrystallized from toluene

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

Procedure: Acetic anhydride (1.25 mL, 12.2 mmol) was added to a solution of 5-amino-2-methyl phenol (1.0 g, 8.1 mmol) in acetic acid (6 mL), and the reaction was refluxed for 5 mins. Then the reaction mixture was cooled to room temperature and the product was solidified. It was filtered off and washed with water (4 mL) and dried to obtain the product along with the trace amount of O-acylated product. The mixture, to which was added 3-bromophenetole (1.33 g, 6.6 mmol) and Cs2CO3 (2.927 g, 9.0 mmol) in DMF (10 mL), was stirred overnight at 50° C. The reaction mixture was then diluted with water (10 mL) and extracted with ethyl acetate (3×20 mL). The combined extracts were dried over sodium sulfate and recrystallized from toluene to obtain the pure product 18a in 65% (yield over two steps) as an off-white solid. the reaction was refluxed for 5 mins It was filtered off washed with water (4 mL) dried to obtain the product along with the trace amount of O-acylated product extracted with ethyl acetate (3×20 mL) The combined extracts were dried over sodium sulfate recrystallized from toluene

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

Procedure: The base of compound (56) was reacted with 1-bromo-3-ethoxy-benzene corresponding to the conditions described in Example 1. The base obtained was purified with diisopropyl ether via a silica gel column and was taken up in 2-butanone/ether. After adding trimethylchlorosilane/water, compound (58) was obtained in a yield of 52% theoretical. The base obtained was purified with diisopropyl ether via a silica gel column After adding trimethylchlorosilane/water

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

Procedure: In DMF (96 ml) was dissolved 3-bromophenol (12 g). To the mixture was added potassium carbonate (12.5 g) and then 2-bromoethylethylether (6.7 ml), and the mixture was stirred at room temperature for 16 hours. The reaction mixture was added to water, and the mixture was extracted with ethyl acetate, washed with saturated brine and dried with magnesium sulfate. Under reduced pressure, the solvent was evaporated, and the residue was purified with silica gel column chromatography (hexane/ethyl acetate=12/1) to give 1-bromo-3-ethoxybenzene (11.6 g). the mixture was extracted with ethyl acetate washed with saturated brine dried with magnesium sulfate Under reduced pressure, the solvent was evaporated the residue was purified with silica gel column chromatography (hexane/ethyl acetate=12/1)

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

Procedure: The title Compound was prepared from Compound 274c following the procedure described for the compound of Example 274 but using 3-ethoxybromobenzene instead of 1-bromo-3,5-difluorobenzene and adding 1 molar equivalent of tetrabutylammonium fluoride monohydrate to the starting reaction mixture. After the work-up, the residue was purified by automated flash liquid chromatography (SP1™-Biotage) eluting with PE-EtOAc gradient from PE:EtAc 1:0 to 8:2 affording the title product. Yellow solid. Yield: 46%. to the starting reaction mixture After the work-up, the residue was purified by automated flash liquid chromatography (SP1™-Biotage) eluting with PE-EtOAc gradient from PE

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

Procedure: The title compound was prepared from 3-bromophenetole and 4-bromo-N-methoxy-N-methylbenzamide following the general method of Method 1. The crude product was re-crystallized from methanol affording 0.37 g (47% yield) of the title compound as colorless crystals: mp 68.5-70.1° C.; 1H NMR (400 MHz, CDCl3) δ 7.70-7.60 (m, 4 H), 7.38 (broad t, J=7.6 Hz, 1 H), 7.31-7.27 (m, 2 H), 7.13 (ddd, J=8.2, J=2.3, J=1.2 Hz, 1 H), 4.08 (q, J=7.0 Hz, 2 H), 1.43 (t, J=7.0 Hz, 3 H); 13C NMR (400 MHz, CDCl3) δ 195.5, 159.0, 138.4, 136.4, 131.6, 131.5, 129.3, 127.5, 122.5, 119.5, 114.9, 63.7, 14.7; MS (TSP) m/z 305 (M+1).

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

Procedure: Acetic anhydride (1.25 mL, 12.2 mmol) was added to a solution of 5-amino-2-methyl phenol (1.0 g, 8.1 mmol) in acetic acid (6 mL), and the reaction was refluxed for 5 mins. Then the reaction mixture was cooled to room temperature and the product was solidified. It was filtered off and washed with water (4 mL) and dried to obtain the product along with the trace amount of O-acylated product. The mixture, to which was added 3-bromophenetole (1.33 g, 6.6 mmol) and Cs2CO3 (2.927 g, 9.0 mmol) in DMF (10 mL), was stirred overnight at 50° C. The reaction mixture was then diluted with water (10 mL) and extracted with ethyl acetate (3×20 mL). The combined extracts were dried over sodium sulfate and recrystallized from toluene to obtain the pure product 18a in 65% (yield over two steps) as an off-white solid. the reaction was refluxed for 5 mins It was filtered off washed with water (4 mL) dried to obtain the product along with the trace amount of O-acylated product extracted with ethyl acetate (3×20 mL) The combined extracts were dried over sodium sulfate recrystallized from toluene