1-bromo-2-methylpentane

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: [(R)-2-Hydroxy-1-(4-hydroxy-phenyl)-ethyl]-carbamic acid t-butyl ester (0.700 g 2.77 mmol), 2-methylpentyl bromide (0.548 g, 3.32 mmol) and Cs2CO3 (1.17 g, 3.59 mmol) were combined in DMF (15 ml). The reaction mixture was heated at 70° C. overnight. Saturated NH4Cl was added to quench the reaction. The aqueous layer was extracted with ethyl acetate (3×10 ml). The combined organic layers were washed with brine, then dried over MgSO4, filtered and concentrated to give a white crude solid. The crude product was purified via column chromatography on silica gel (0%-50% ethyl acetate in hexanes) to afford the title compound (0.705 g, 76% yield of 2 steps) as a white solid: 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.21 (d, 2H), 6.89 (d, J=8.6 Hz, 2H), 5.18 (d, J=7.1 Hz, 1H), 4.72 (br. s., 1 H), 3.81 (dd, J=9.0, 5.7 Hz, 3H), 3.72 (m, 1H), 3.49 (s, 2H), 2.54 (br. s., 1H), 1.95 (m, 1H), 1.35 (m, 11H), 1.02 (d, J=6.8 Hz, 3H), 0.93 (m, 3H); LCMS (ESI) m/e 338.2 [(M+H), calcd for C19H32NO4 338.5]. to quench the reaction The aqueous layer was extracted with ethyl acetate (3×10 ml) The combined organic layers were washed with brine dried over MgSO4 filtered concentrated to give a white crude solid The crude product was purified via column chromatography on silica gel (0%-50% ethyl acetate in hexanes)

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

Procedure: Sodium metal (6.99 g, 304 mmol) was dissolved in dry methanol (120 ml) under Ar to give a 2.5M solution of sodium methoxide. A solution of 4-methoxyphenol (31.4 g, 253 mmol) in dry methanol (150 ml) was added and this mixture was heated to reflux for 30 min. After cooling to room temperature, a solution of 1-bromo-2-methylpentane (46.0 g, 279 mmol) in dry methanol (100 ml) was added. The mixture was then heated to reflux for 16 hours. The solvent was removed in vacuo, the residue dissolved in ether (200 ml), washed with dilute aqueous sodium hydroxide (250 ml) and water (500 ml), dried over MgSO4 and concentrated in vacuo again. Distillation at 80° C./0.5 mm Hg afforded 14.0g (27%) 1-methoxy-4-(2'-methylpentyloxy)benzene, 1H NMR (250.1 MHz , CDCl3): δ=0.94 (t,3H), 1.02 (d, 3H), 1.16-1.56 (m, 4H), 1.93 (m, 1H), 3.64-3.82 (m, 2H), 3.77 (s, 3H), 6.81-6.89 (m, 4H), 13C NMR (100.6 MHz, CDCl3): δ=14.3, 17.0 (both CH3), 20.1, 35.8 (both CH2), 33.0 (CH), 55.7 (OCH3), 73.9 (OCH2), 114.6, 115.4 (arom. CH), 153.5, 153.6 (ipso C). IR(film): 2956(m), 1509(s), 1232(s), 1045(m), 824 (m) cm-1, MS(EI): m/z (%)=208 (100), 124 (32), Calcd. for C13H20O2 : C 74.96, H 9.68 found: C 75.03, H 9.70. this mixture was heated to reflux for 30 min The mixture was then heated to reflux for 16 hours The solvent was removed in vacuo the residue dissolved in ether (200 ml) washed with dilute aqueous sodium hydroxide (250 ml) and water (500 ml) dried over MgSO4 concentrated in vacuo again Distillation at 80° C./0.5 mm Hg

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

Procedure: Sodium metal (6.99 g, 304 mmol) was dissolved in dry methanol (120 ml) under Ar to give a 2.5M solution of sodium methoxide. A solution of 4-methoxyphenol (31.4 g, 253 mmol) in dry methanol (150 ml) was added and this mixture was heated to reflux for 30 min. After cooling to room temperature, a solution of 1-bromo-2-methylpentane (46.0 g, 279 mmol) in dry methanol (100 ml) was added. The mixture was then heated to reflux for 16 hours. The solvent was removed in vacuo, the residue dissolved in ether (200 ml), washed with dilute aqueous sodium hydroxide (250 ml) and water (500 ml), dried over MgSO4 and concentrated in vacuo again. Distillation at 80° C./0.5 mm Hg afforded 14.0g (27%) 1-methoxy-4-(2'-methylpentyloxy)benzene, 1H NMR (250.1 MHz , CDCl3): δ=0.94 (t,3H), 1.02 (d, 3H), 1.16-1.56 (m, 4H), 1.93 (m, 1H), 3.64-3.82 (m, 2H), 3.77 (s, 3H), 6.81-6.89 (m, 4H), 13C NMR (100.6 MHz, CDCl3): δ=14.3, 17.0 (both CH3), 20.1, 35.8 (both CH2), 33.0 (CH), 55.7 (OCH3), 73.9 (OCH2), 114.6, 115.4 (arom. CH), 153.5, 153.6 (ipso C). IR(film): 2956(m), 1509(s), 1232(s), 1045(m), 824 (m) cm-1, MS(EI): m/z (%)=208 (100), 124 (32), Calcd. for C13H20O2 : C 74.96, H 9.68 found: C 75.03, H 9.70. this mixture was heated to reflux for 30 min The mixture was then heated to reflux for 16 hours The solvent was removed in vacuo the residue dissolved in ether (200 ml) washed with dilute aqueous sodium hydroxide (250 ml) and water (500 ml) dried over MgSO4 concentrated in vacuo again Distillation at 80° C./0.5 mm Hg

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

Procedure: Sodium metal (6.99 g, 304 mmol) was dissolved in dry methanol (120 ml) under Ar to give a 2.5M solution of sodium methoxide. A solution of 4-methoxyphenol (31.4 g, 253 mmol) in dry methanol (150 ml) was added and this mixture was heated to reflux for 30 min. After cooling to room temperature, a solution of 1-bromo-2-methylpentane (46.0 g, 279 mmol) in dry methanol (100 ml) was added. The mixture was then heated to reflux for 16 hours. The solvent was removed in vacuo, the residue dissolved in ether (200 ml), washed with dilute aqueous sodium hydroxide (250 ml) and water (500 ml), dried over MgSO4 and concentrated in vacuo again. Distillation at 80° C./0.5 mm Hg afforded 14.0 g (27%) 1-methoxy-4-(2'-methylpentyloxy)benzene, 1H NMR (250.1 MHz, CDCl3): δ=0.94(t,3 H), 1.02 (d, 3 H), 1.16-1.56 (m, 4 H), 1.93 (m, 1 H), 3.64-3.82 (m, 2 H), 3.77 (s, 3 H), 6.81-6.89 (m, 4 H), 13C NMR (100.6 MHz, CDCl3): δ=14.3, 17.0 (both CH3), 20.1, 35.8 (both CH2), 33.0 (CH), 55.7 (OCH3), 73.9 (OCH2), 114.6, 115.4 (arom. CH), 153.5, 153.6 (ipso C). IR(film): 2956(m), 1509(s), 1232(s), 1045(m), 824(m) cm-1, MS(EI) :m/z (%)=208 (100), 124 (32), Calcd. for C13H20O2 : C 74.96, H 9.68 found: C 75.03, H 9.70. this mixture was heated to reflux for 30 min The mixture was then heated to reflux for 16 hours The solvent was removed in vacuo the residue dissolved in ether (200 ml) washed with dilute aqueous sodium hydroxide (250 ml) and water (500 ml) dried over MgSO4 concentrated in vacuo again Distillation at 80° C./0.5 mm Hg

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

Procedure: Sodium metal (6.99 g, 304 mmol) was dissolved in dry methanol (120 ml) under Ar to give a 2.5M solution of sodium methoxide. A solution of 4-methoxyphenol (31.4 g, 253 mmol) in dry methanol (150 ml) was added and this mixture was heated to reflux for 30 min. After cooling to room temperature, a solution of 1-bromo-2-methylpentane (46.0 g, 279 mmol) in dry methanol (100 ml) was added. The mixture was then heated to reflux for 16 hours. The solvent was removed in vacuo, the residue dissolved in ether (200 ml), washed with dilute aqueous sodium hydroxide (250 ml) and water (500 ml), dried over MgSO4 and concentrated in vacuo again. Distillation at 80° C./0.5 mm Hg afforded 14.0 g (27%) 1-methoxy-4-(2'-methylpentyloxy) benzene, 1H NMR (250.1 MHz, CDCl3): δ=0.94(t,3H), 1.02 (d, 3H), 1.16-1.56 (m, 4H), 1.93 (m, 1H), 3.64-3.82 (m, 2H), 3.77 (s, 3H), 6.81-6.89 (m, 4H), 13C NMR (100.6 MHz, CDCl3): δ=14.3, 17.0 (both CH3), 20.1, 35.8 (both CH2), 33.0 (CH), 55.7 (OCH3), 73.9 (OCH2), 114.6, 115.4 (arom. CH), 153.5, 153.6 (ipso C). IR(film): 2956(m), 1509(s), 1232(s), 1045(m), 824(m) cm-1, MS(EI): m/z (%)=208 (100), 124 (32), Calcd. for C13H20O2 : C 74.96, H 9.68 found: C 75.03, H 9.70. this mixture was heated to reflux for 30 min The mixture was then heated to reflux for 16 hours The solvent was removed in vacuo the residue dissolved in ether (200 ml) washed with dilute aqueous sodium hydroxide (250 ml) and water (500 ml) dried over MgSO4 concentrated in vacuo again Distillation at 80° C./0.5 mm Hg

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

Procedure: Sodium metal (6.99 g, 304 mmol) was dissolved in dry methanol (120 ml) under Ar to give a 2.5M solution of sodium methoxide. A solution of 4-methoxyphenol (31.4 g, 253 mmol) in dry methanol (150 ml) was added and this mixture was heated to reflux for 30 min. After cooling to room temperature, a solution of 1-bromo-2-methylpentane (46.0 g, 279 mmol) in dry methanol (100 ml) was added. The mixture was then heated to reflux for 16 hours. The solvent was removed in vacuo, the residue dissolved in ether (200 ml), washed with dilute aqueous sodium hydroxide (250 ml) and water (500 ml), dried over MgSO4 and concentrated in vacuo again. Distillation at 80° C./0.5 mm Hg afforded 14.0 g (27%) 1-methoxy-4-(2'-methylpentyloxy)benzene, 1H NMR (250.1 MHz, CDCl3): δ=0.94(t,3H), 1.02 (d, 3H), 1.16-1.56 (m, 4H), 1.93 (m, 1H), 3.64-3.82 (m, 2H), 3.77 (s, 3H), 6.81-6.89 (m, 4H), 13C NMR (100.6 MHz, CDCl3): δ=14.3, 17.0 (both CH3), 20.1, 35.8 (both CH2), 33.0 (CH), 55.7 (OCH3), 73.9 (OCH2), 114.6, 115.4 (arom. CH), 153.5, 153.6 (ipso C). IR(film): 2956(m), 1509(s), 1232(s), 1045(m), 824(m) cm-1, MS(EI): m/z (%)=208 (100), 124 (32), Calcd. for C13H20O2 : C 74.96, H 9.68 found: C 75.03, H 9.70. this mixture was heated to reflux for 30 min The mixture was then heated to reflux for 16 hours The solvent was removed in vacuo the residue dissolved in ether (200 ml) washed with dilute aqueous sodium hydroxide (250 ml) and water (500 ml) dried over MgSO4 concentrated in vacuo again Distillation at 80° C./0.5 mm Hg

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: [(R)-2-Hydroxy-1-(4-hydroxy-phenyl)-ethyl]-carbamic acid t-butyl ester (0.700 g 2.77 mmol), 2-methylpentyl bromide (0.548 g, 3.32 mmol) and Cs2CO3 (1.17 g, 3.59 mmol) were combined in DMF (15 ml). The reaction mixture was heated at 70° C. overnight. Saturated NH4Cl was added to quench the reaction. The aqueous layer was extracted with ethyl acetate (3×10 ml). The combined organic layers were washed with brine, then dried over MgSO4, filtered and concentrated to give a white crude solid. The crude product was purified via column chromatography on silica gel (0%-50% ethyl acetate in hexanes) to afford the title compound (0.705 g, 76% yield of 2 steps) as a white solid: 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.21 (d, 2H), 6.89 (d, J=8.6 Hz, 2H), 5.18 (d, J=7.1 Hz, 1H), 4.72 (br. s., 1 H), 3.81 (dd, J=9.0, 5.7 Hz, 3H), 3.72 (m, 1H), 3.49 (s, 2H), 2.54 (br. s., 1H), 1.95 (m, 1H), 1.35 (m, 11H), 1.02 (d, J=6.8 Hz, 3H), 0.93 (m, 3H); LCMS (ESI) m/e 338.2 [(M+H), calcd for C19H32NO4 338.5]. to quench the reaction The aqueous layer was extracted with ethyl acetate (3×10 ml) The combined organic layers were washed with brine dried over MgSO4 filtered concentrated to give a white crude solid The crude product was purified via column chromatography on silica gel (0%-50% ethyl acetate in hexanes)

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

Procedure: Sodium metal (6.99 g, 304 mmol) was dissolved in dry methanol (120 ml) under Ar to give a 2.5M solution of sodium methoxide. A solution of 4-methoxyphenol (31.4 g, 253 mmol) in dry methanol (150 ml) was added and this mixture was heated to reflux for 30 min. After cooling to room temperature, a solution of 1-bromo-2-methylpentane (46.0 g, 279 mmol) in dry methanol (100 ml) was added. The mixture was then heated to reflux for 16 hours. The solvent was removed in vacuo, the residue dissolved in ether (200 ml), washed with dilute aqueous sodium hydroxide (250 ml) and water (500 ml), dried over MgSO4 and concentrated in vacuo again. Distillation at 80° C./0.5 mm Hg afforded 14.0g (27%) 1-methoxy-4-(2'-methylpentyloxy)benzene, 1H NMR (250.1 MHz , CDCl3): δ=0.94 (t,3H), 1.02 (d, 3H), 1.16-1.56 (m, 4H), 1.93 (m, 1H), 3.64-3.82 (m, 2H), 3.77 (s, 3H), 6.81-6.89 (m, 4H), 13C NMR (100.6 MHz, CDCl3): δ=14.3, 17.0 (both CH3), 20.1, 35.8 (both CH2), 33.0 (CH), 55.7 (OCH3), 73.9 (OCH2), 114.6, 115.4 (arom. CH), 153.5, 153.6 (ipso C). IR(film): 2956(m), 1509(s), 1232(s), 1045(m), 824 (m) cm-1, MS(EI): m/z (%)=208 (100), 124 (32), Calcd. for C13H20O2 : C 74.96, H 9.68 found: C 75.03, H 9.70. this mixture was heated to reflux for 30 min The mixture was then heated to reflux for 16 hours The solvent was removed in vacuo the residue dissolved in ether (200 ml) washed with dilute aqueous sodium hydroxide (250 ml) and water (500 ml) dried over MgSO4 concentrated in vacuo again Distillation at 80° C./0.5 mm Hg