ethyl 2-[4-(bromomethyl)phenyl]-2-methylpropanoate

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

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

Procedure: NaH (60% by weight in oil, 23 mg, 0.55 mmol) was washed with DMF (5 mL) and fresh DMF (5 mL) was added. The reaction was cooled to 0° C. and a solution of {3-[(pyridine-3-sulfonylamino)-methyl]-phenoxy}-acetic acid tert-butyl ester (184 mg, 0.486 mmol) in DMF (1 mL) was added. The reaction was stirred for 1 h and 2-(4-bromomethyl-phenyl)-2-methyl-propionic acid ethyl ester (145 mg, 0.51 mmol) in DMF (1 mL) was added. The reaction was warmed to room temperature and was heated at 100° C. for 2 h. Water was added and the aqueous solution was washed with EtOAc (3×). The combined organic solutions were washed with water (5×), dried (MgSO4), filtered and concentrated. Flash chromatography (2:1 hexanes:EtOAc) provided 2-(4-{[(3-tert-butoxycarbonylmethoxy-benzyl)-(pyridine-3-sulfonyl)-amino]-methyl}-phenyl)-2-methyl-propionic acid ethyl ester (138 mg). 1H NMR (400 MHz, CDCl3) δ 9.01 (s, 1H), 8.76 (m, 1H), 7.97 (m, 1H), 7.40 (m, 1H), 7.19 (d, 2H), 7.13 (m, 1H), 7.02 (d, 2H), 6.76 (m, 1H), 6.67 (m, 2H), 4.41 (s, 2H), 4.33 (s, 4H), 4.10 (q, 2H), 1.52 (s, 6H), 1.49 (s, 9H), 1.17 (t, 3H). was added The reaction was warmed to room temperature was heated at 100° C. for 2 h the aqueous solution was washed with EtOAc (3×) The combined organic solutions were washed with water (5×) dried (MgSO4) filtered concentrated

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

Procedure: To a solution of 2-methyl-2-p-tolyl-propionic acid ethyl ester (263 mg, 1.27 mmol) and N-bromosuccinimide (272 mg, 1.53 mmol) in CCl4 (15 mL) was added 1,1′-azobis(cyclohexanecarbonitrile) (15.5 mg, 0.06 mmol). The reaction was heated at reflux for 1 h and was diluted with water and CH2Cl2. The layers were separated and the aqueous layer was washed with CH2Cl2 (3×). The combined organic solutions were dried (MgSO4), filtered, and concentrated. Medium pressure chromatography (95:5 hexanes:EtOAc) provided 2-(4-bromomethyl-phenyl)-2-methyl-propionic acid ethyl ester (354 mg). 1H NMR (400 MHz, CDCl3) δ 7.31 (m, 4H), 4.47 (s, 2H), 4.10 (q, 2H), 1.54 (s, 6H), 1.17 (t, 3H). The reaction was heated at reflux for 1 h The layers were separated the aqueous layer was washed with CH2Cl2 (3×) The combined organic solutions were dried (MgSO4) filtered concentrated

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

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

Procedure: NaH (60% by weight in oil, 23 mg, 0.55 mmol) was washed with DMF (5 mL) and fresh DMF (5 mL) was added. The reaction was cooled to 0° C. and a solution of {3-[(pyridine-3-sulfonylamino)-methyl]-phenoxy}-acetic acid tert-butyl ester (184 mg, 0.486 mmol) in DMF (1 mL) was added. The reaction was stirred for 1 h and 2-(4-bromomethyl-phenyl)-2-methyl-propionic acid ethyl ester (145 mg, 0.51 mmol) in DMF (1 mL) was added. The reaction was warmed to room temperature and was heated at 100° C. for 2 h. Water was added and the aqueous solution was washed with EtOAc (3×). The combined organic solutions were washed with water (5×), dried (MgSO4), filtered and concentrated. Flash chromatography (2:1 hexanes:EtOAc) provided 2-(4-{[(3-tert-butoxycarbonylmethoxy-benzyl)-(pyridine-3-sulfonyl)-amino]-methyl}-phenyl)-2-methyl-propionic acid ethyl ester (138 mg). 1H NMR (400 MHz, CDCl3) δ 9.01 (s, 1H), 8.76 (m, 1H), 7.97 (m, 1H), 7.40 (m, 1H), 7.19 (d, 2H), 7.13 (m, 1H), 7.02 (d, 2H), 6.76 (m, 1H), 6.67 (m, 2H), 4.41 (s, 2H), 4.33 (s, 4H), 4.10 (q, 2H), 1.52 (s, 6H), 1.49 (s, 9H), 1.17 (t, 3H). was added The reaction was warmed to room temperature was heated at 100° C. for 2 h the aqueous solution was washed with EtOAc (3×) The combined organic solutions were washed with water (5×) dried (MgSO4) filtered concentrated

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

Procedure: To a solution of 2-methyl-2-p-tolyl-propionic acid ethyl ester (263 mg, 1.27 mmol) and N-bromosuccinimide (272 mg, 1.53 mmol) in CCl4 (15 mL) was added 1,1′-azobis(cyclohexanecarbonitrile) (15.5 mg, 0.06 mmol). The reaction was heated at reflux for 1 h and was diluted with water and CH2Cl2. The layers were separated and the aqueous layer was washed with CH2Cl2 (3×). The combined organic solutions were dried (MgSO4), filtered, and concentrated. Medium pressure chromatography (95:5 hexanes:EtOAc) provided 2-(4-bromomethyl-phenyl)-2-methyl-propionic acid ethyl ester (354 mg). 1H NMR (400 MHz, CDCl3) δ 7.31 (m, 4H), 4.47 (s, 2H), 4.10 (q, 2H), 1.54 (s, 6H), 1.17 (t, 3H). The reaction was heated at reflux for 1 h The layers were separated the aqueous layer was washed with CH2Cl2 (3×) The combined organic solutions were dried (MgSO4) filtered concentrated

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

Procedure: The title compound was prepared from 3-[3-benzyl-8-(trifluoromethyl)quinolin-4-yl]phenol and 2-(4-Bromomethyl-phenyl)-2-methyl-propionic acid ethyl ester as in the procedure of Example 43. MS m/z 570;

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

Procedure: NaH (60% by weight in oil, 23 mg, 0.55 mmol) was washed with DMF (5 mL) and fresh DMF (5 mL) was added. The reaction was cooled to 0° C. and a solution of {3-[(pyridine-3-sulfonylamino)-methyl]-phenoxy}-acetic acid tert-butyl ester (184 mg, 0.486 mmol) in DMF (1 mL) was added. The reaction was stirred for 1 h and 2-(4-bromomethyl-phenyl)-2-methyl-propionic acid ethyl ester (145 mg, 0.51 mmol) in DMF (1 mL) was added. The reaction was warmed to room temperature and was heated at 100° C. for 2 h. Water was added and the aqueous solution was washed with EtOAc (3×). The combined organic solutions were washed with water (5×), dried (MgSO4), filtered and concentrated. Flash chromatography (2:1 hexanes:EtOAc) provided 2-(4-{[(3-tert-butoxycarbonylmethoxy-benzyl)-(pyridine-3-sulfonyl)-amino]-methyl}-phenyl)-2-methyl-propionic acid ethyl ester (138 mg). 1H NMR (400 MHz, CDCl3) δ 9.01 (s, 1H), 8.76 (m, 1H), 7.97 (m, 1H), 7.40 (m, 1H), 7.19 (d, 2H), 7.13 (m, 1H), 7.02 (d, 2H), 6.76 (m, 1H), 6.67 (m, 2H), 4.41 (s, 2H), 4.33 (s, 4H), 4.10 (q, 2H), 1.52 (s, 6H), 1.49 (s, 9H), 1.17 (t, 3H). was added The reaction was warmed to room temperature was heated at 100° C. for 2 h the aqueous solution was washed with EtOAc (3×) The combined organic solutions were washed with water (5×) dried (MgSO4) filtered concentrated

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

Procedure: To a solution of 2-methyl-2-p-tolyl-propionic acid ethyl ester (263 mg, 1.27 mmol) and N-bromosuccinimide (272 mg, 1.53 mmol) in CCl4 (15 mL) was added 1,1′-azobis(cyclohexanecarbonitrile) (15.5 mg, 0.06 mmol). The reaction was heated at reflux for 1 h and was diluted with water and CH2Cl2. The layers were separated and the aqueous layer was washed with CH2Cl2 (3×). The combined organic solutions were dried (MgSO4), filtered, and concentrated. Medium pressure chromatography (95:5 hexanes:EtOAc) provided 2-(4-bromomethyl-phenyl)-2-methyl-propionic acid ethyl ester (354 mg). 1H NMR (400 MHz, CDCl3) δ 7.31 (m, 4H), 4.47 (s, 2H), 4.10 (q, 2H), 1.54 (s, 6H), 1.17 (t, 3H). The reaction was heated at reflux for 1 h The layers were separated the aqueous layer was washed with CH2Cl2 (3×) The combined organic solutions were dried (MgSO4) filtered concentrated