[2-(hydroxymethyl)phenyl]boronic acid

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

Procedure: A mixture of 1-propanol (7.5 mL) and water (2.5 mL) was purged with nitrogen for 5 minutes. To the solution were added 4-bromo-1H-imidazole (146.97 mg, 1 mmol), 2-(hydroxyl-methyl)phenylboronic acid (190 mg, 1.25 mmol), Pd(OAc)2 (11.2 mg, 0.05 mmol), PPh3 (39.3 mg, 0.15 mmol) and potassium carbonate (276 mg, 2.0 mmol). After stirring at 85° C. for 16 h, the mixture was allowed to cool to room temperature and was partitioned between EtOAc (30 mL) and water (15 mL). The aqueous layer was extracted with EtOAc (2×20 mL) and the combined organic layers were washed with water, brine, and dried over sodium sulfate. The solvent was removed under reduced pressure and the crude product was purified by flash column chromatography on silica gel to afford the pure product (62 mg, 37% yield). 1H NMR: 4.48 (s, 2H), 6.25 (br s, 1H), 7.18-7.28 (m, 2H), 7.39-7.47 (m, 2H), 7.62 (d, 1H, J=7.0 Hz), 7.80 (d, 1H), 12.30 (br s, 1H). was purged with nitrogen for 5 minutes to cool to room temperature was partitioned between EtOAc (30 mL) and water (15 mL) The aqueous layer was extracted with EtOAc (2×20 mL) the combined organic layers were washed with water, brine dried over sodium sulfate The solvent was removed under reduced pressure the crude product was purified by flash column chromatography on silica gel

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

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of Example 57c (0.300 g, 0.568 mmoles) in DMF (3 ml), ethanol (1.5 ml) and water (1.5 ml), 2-Hydroxymethylphenylboronic acid (0.173 g, 1.137 mmoles) and sodium carbonate (0.301 g, 2.844 mmoles) were added and the system is degassed for 30 min. Tetrakistriphenylphosphine Palladium (0.129 g, 0.112 mmoles) was added under nitrogen atmosphere and heated to 80° C. After 12 h, the reaction mixture was celite filtered, concentrated and extracted with ethyl acetate. The organic layer was dried over sodium sulphate and concentrated under reduced pressure. The crude product was purified by column chromatography with methanol: dichloromethane to afford the title compound as off-white solid (0.090 g, 31% yield). MP: 185-189° C. 1H-NMR (δ ppm, DMSO-d6, 400 MHz): δ 8.09(s,1H), 8.04(dd, J=7.9,1.4 Hz, 1H), 7.84(m,1H), 7.66-7.35(m,10H), 7.17(dt, J=10.8,1.4 Hz, 1H), 7.04(m,1H), 6.01(q, J=6.7 Hz, 1H), 5.13(t, J=5.7 Hz, 1H), 4.54(m,2H), 1.87(d, J=7.1 Hz, 3H). Mass: 508.16(M++1). the system is degassed for 30 min concentrated extracted with ethyl acetate The organic layer was dried over sodium sulphate concentrated under reduced pressure The crude product was purified by column chromatography with methanol

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 0.64 ml of 2 M aqueous sodium carbonate solution and 17.5 mg (0.02 mmol) of PdCl2(dppf) are added to a mixture of 150 mg (0.43 mmol) of N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-7-bromo-1-benzofuran-2-carboxamide hydrochloride (Example 30A) and 65.3 mg (0.43 mmol) of 2-(hydroxymethyl)phenylboronic acid in 1.5 ml of DMF. The reaction mixture is heated at 90° C. for 18 h and then filtered through kieselguhr and evaporated to dryness. Purification of the crude product by preparative HPLC, subsequent addition of a 3:1 mixture of acetonitrile and 1N hydrochloric acid, concentration and drying under high vacuum result in 13 mg (7.1% of theory) of the title compound. filtered through kieselguhr evaporated to dryness Purification of the crude product by preparative HPLC, subsequent addition of a 3:1 mixture of acetonitrile and 1N hydrochloric acid, concentration drying under high vacuum