2-bromo-4-ethylphenol

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

Procedure: A solution was prepared by dissolving 105 g of 4-ethylphenol into 500 ml of chloroform. The solution was cooled by ice water bath, followed by dropwise addition of 45 ml of bromine while stirring. The addition was took 1 hour. Then, the reaction mixture was cooled by an ice water bath while stirring for 4 hours, moved into a separatory funnel to wash with water, an aqueous solution saturated with NaCl, 10% water solution of sodium hydrogencarbonate and an aqueous solution saturated with NaCl in turn, and dried with magnesium sulfate anhydride. The solvent in the reactant was distilled off under reduced pressure to yield 173 g of light brown and oily 2-bromo-4-ethylphenol. A solution was prepared The solution was cooled by ice water bath The addition Then, the reaction mixture was cooled by an ice water bath while stirring for 4 hours moved into a separatory funnel to wash with water an aqueous solution saturated with NaCl, 10% water solution of sodium hydrogencarbonate and an aqueous solution saturated with NaCl in turn, and dried with magnesium sulfate anhydride The solvent in the reactant was distilled off under reduced pressure

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

Procedure: 8.41 ml of bromine in 100 ml of CHCl3 were added dropwise within 2 hrs. to a solution, cooled to 0° C., of 20 g of 4-ethylphenol in 200 ml of CHCl3 and 100 ml of MeOH. The reaction mixture was left to warm to room temperature and was concentrated. The product was isolated by extraction. There were obtained 33.14 g of 2-bromo-4-ethyl-phenol as a light brown oil. The reaction mixture was left was concentrated The product was isolated by extraction

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

Procedure: 8.41 ml of bromine in 100 ml of CHCl3 were added dropwise within 2 hrs. to a solution, cooled to 0° C., of 20 g of 4-ethylphenol in 200 ml of CHCl3 and 100 ml of MeOH. The reaction mixture was left to warm to room temperature and was concentrated. The product was isolated by extraction. There were obtained 33.14 g of 2-bromo-4-ethyl-phenol as a light brown oil. The reaction mixture was left was concentrated The product was isolated by extraction

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

Procedure: 8.41 ml of bromine in 100 ml of CHCl3 were added dropwise within 2 hrs. to a solution, cooled to 0° C., of 20 g of 4-ethylphenol in 200 ml of CHCl3 and 100 ml of MeOH. The reaction mixture was left to warm to room temperature and was concentrated. The product was isolated by extraction. There were obtained 33.14 g of 2-bromo-4-ethyl-phenol as a light brown oil. The reaction mixture was left was concentrated The product was isolated by extraction

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

Procedure: Bromine (11.6 mL, 0.23 mol) was added slowly to a cooled 0° C. of 4-ethylphenol (2 g, 0.21 mol) dissolved in CH2Cl2 (125 mL). After the addition was complete the reaction mixture was stirred for 5 mins and then quenched with 1N NaOH. The reaction mixture was diluted with H2O and the layers separated. The organic layer was concentrated to an orange oil. Purification by flash column chromatography (0% to 5% EtOAc in hexanes) gave the title compound as a clear oil (4 g, 98%). 1H NMR (400 MHz, CDCl3): δ 1.20 (t, J=7.6 Hz, 3 H), 2.58 (q, J=7.5 Hz, 2 H), 5.36 (s, 1 H), 6.93 (d, J=8.3 Hz, 1 H), 7.03 (d, J=8.3 Hz, 1 H), 7.28 (s, 1 H). After the addition quenched with 1N NaOH The reaction mixture was diluted with H2O the layers separated The organic layer was concentrated to an orange oil Purification by flash column chromatography (0% to 5% EtOAc in hexanes)

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

Procedure: Bromine (11.6 mL, 0.23 mol) was added slowly to a cooled 0° C. of 4-ethylphenol (2 g, 0.21 mol) dissolved in CH2Cl2 (125 mL). After the addition was complete the reaction mixture was stirred for 5 mins and then quenched with 1N NaOH. The reaction mixture was diluted with H2O and the layers separated. The organic layer was concentrated to an orange oil. Purification by flash column chromatography (0% to 5% EtOAc in hexanes) gave the title compound as a clear oil (4 g, 98%). 1H NMR (400 MHz, CDCl3): δ 1.20 (t, J=7.6 Hz, 3 H), 2.58 (q, J=7.5 Hz, 2 H), 5.36 (s, 1 H), 6.93 (d, J=8.3 Hz, 1 H), 7.03 (d, J=8.3 Hz, 1 H), 7.28 (s, 1 H). After the addition quenched with 1N NaOH The reaction mixture was diluted with H2O the layers separated The organic layer was concentrated to an orange oil Purification by flash column chromatography (0% to 5% EtOAc in hexanes)

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

Procedure: Potassium carbonate (8.25 g, 60 mol) followed by 2-bromoethyl methyl ether (1.87 mL, 20 mmol) were added to a solution of 2-bromo-4-ethyl-phenol (4 g, 20 mmol, from step 1 of Example B(98)) in DMF (25 mL). The mixture was stirred for 20 hours and then partitioned between 1N HCl and EtOAc. The organic layers were washed with brine, dried over Na2SO4 and concentrated. The crude yellow oil was purified by flash column chromatography (0% to 10% EtOAc in hexanes) to give the desired product (4.63 g, 90%). 1H NMR (400 MHz, CDCl3): δ 1.20 (t, J=7.6 Hz, 3 H), 2.57 (q, J=7.6 Hz, 2 H), 3.48 (s, 3 H), 3.79 (t, J=5.1 Hz, 2 H), 4.15 (t, J=4.8 Hz, 2 H), 6.85 (d, J=8.3 Hz, 1 H), 7.06 (dd, J=8.3, 2.3 Hz, 1 H), 7.37 (d, J=2.3 Hz, 1 H). partitioned between 1N HCl and EtOAc The organic layers were washed with brine dried over Na2SO4 concentrated The crude yellow oil was purified by flash column chromatography (0% to 10% EtOAc in hexanes)

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

Procedure: A solution was prepared by dissolving 105 g of 4-ethylphenol into 500 ml of chloroform. The solution was cooled by ice water bath, followed by dropwise addition of 45 ml of bromine while stirring. The addition was took 1 hour. Then, the reaction mixture was cooled by an ice water bath while stirring for 4 hours, moved into a separatory funnel to wash with water, an aqueous solution saturated with NaCl, 10% water solution of sodium hydrogencarbonate and an aqueous solution saturated with NaCl in turn, and dried with magnesium sulfate anhydride. The solvent in the reactant was distilled off under reduced pressure to yield 173 g of light brown and oily 2-bromo-4-ethylphenol. A solution was prepared The solution was cooled by ice water bath The addition Then, the reaction mixture was cooled by an ice water bath while stirring for 4 hours moved into a separatory funnel to wash with water an aqueous solution saturated with NaCl, 10% water solution of sodium hydrogencarbonate and an aqueous solution saturated with NaCl in turn, and dried with magnesium sulfate anhydride The solvent in the reactant was distilled off under reduced pressure

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

Procedure: Starting from 2-bromo-4-ethyl-phenol (example B.a5) and commercially available bromomethyl-cyclopropane the title compound is obtained as colorless oil after distillation at 10 mbar.

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

Procedure: Starting from 2-bromo-4-ethyl-phenol (example B.a5) and commercially available bromomethyl-cyclopropane the title compound is obtained as colorless oil after distillation at 10 mbar.

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 4-ethylphenol (10.0 g, 82.0 mmol) in acetonitrile (250 mL) cooled to 0° C. was slowly added N-bromosuccinimide (16.0 g, 90 mmol) and the reaction mixture was allowed to stir at 0° C. for 1 h. The solvent was removed in vacuo and the reaction mixture was diluted with ice water (500 mL) and diethyl ether (500 mL). A solid precipitate was removed via filtration and the aqueous phase was separated and extracted with ethyl ether (2×200 mL). The combined organic extracts were washed with saturated aqueous sodium chloride (400 mL), dried (magnesium sulfate) and the solvent was removed in vacuo to give a crude oil. Purification by flash column chromatography (silica, ethyl acetate:hexanes 1:9) gave 8.35 g (51%). Treatment of 2-bromo-4-ethylphenol (8.35 g, 41.0 mmol) with potassium carbonate (14.3 g, 100 mmol) and allyl bromide (6.57 g, 130 mmol), followed by refluxing the resultant allyl ether in mesitylene generally according to the procedure described for Intermediate 8 provided 2-allyl-6-bromo-4-ethylphenol. Treatment of 2-allyl-6-bromo-4-ethylphenol (5.18, 22.0 mmol) with 3-chloroperoxybenzoic acid (8.60 g, 33.0 mmol, 77%) followed by potassium carbonate (7.4 g, 55.0 mmol) generally according to the procedure described for Intermediate 9 afforded 3.94 g (70%) of (±)-(7-bromo-5-ethyl-2,3-dihydro-1-benzofuran-2-yl)methanol. Treatment of (±)-(7-bromo-5-ethyl-2,3-dihydro-1-benzofuran-2-yl)methanol (3.94 g, 15.0 mmol) with p-toluenesulfonyl chloride (3.5 g, 18.0 mol) generally according to the procedure described for Intermediate 10 gave 5.78 g (92%) of (±)-(7-bromo-5-ethyl-2,3-dihydro-1-benzofuran-2-yl)methyl 4-methylbenzenesulfonate as a colorless oil. Treatment of (±)-(7-bromo-5-ethyl-2,3-dihydro-1-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.30 g, 0.73 mmol) and 2-methylphenylboronic acid (0.30 g, 2.19 mmol) generally according to the procedure described for Intermediate 35 afforded 0.30 g, (97%) of (±)-(5-ethyl-7-phenyl-2,3-dihydro-1-benzofuran-2-yl)methyl 4-methylbenzenesulfonate. Treatment of the tosylate with sodium azide (0.23 g, 3.55 mmol) generally according to the procedure described for Intermediate 98 afforded 0.16 g (77%) of (±)-2-(azidomethyl)-5-ethyl-7-phenyl-2,3-dihydro-1-benzofuran. Treatment of (±)-2-(azidomethyl)-5-ethyl-7-phenyl-2,3-dihydro-1-benzofuran with polymer-supported triphenylphosphine (0.786 g, 0.869 mmol) according to the procedure described in Example 154 afforded 0.009 g (4%) of (±)-[(5-ethyl-7-phenyl-2,3-dihydro-1-benzofuran-2-yl)methyl]amine as a white solid, hydrochloride salt. mp 198° C. (dec). The solvent was removed in vacuo the reaction mixture was diluted with ice water (500 mL) and diethyl ether (500 mL) A solid precipitate was removed via filtration the aqueous phase was separated extracted with ethyl ether (2×200 mL) The combined organic extracts were washed with saturated aqueous sodium chloride (400 mL) dried (magnesium sulfate) the solvent was removed in vacuo to give a crude oil Purification by flash column chromatography (silica, ethyl acetate:hexanes 1:9) gave 8.35 g (51%)

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

Procedure: 8.41 ml of bromine in 100 ml of CHCl3 were added dropwise within 2 hrs. to a solution, cooled to 0° C., of 20 g of 4-ethylphenol in 200 ml of CHCl3 and 100 ml of MeOH. The reaction mixture was left to warm to room temperature and was concentrated. The product was isolated by extraction. There were obtained 33.14 g of 2-bromo-4-ethyl-phenol as a light brown oil. The reaction mixture was left was concentrated The product was isolated by extraction