[4-(hydroxymethyl)phenyl]methanol

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:; See reaction.notes.procedure_details.

Procedure: To a solution of 1-isocyanatonaphthalene (1.69 g, 10 mmol) and 1,4-phenylene-dimethanol (4.14 g, 30 mmol) in anhydrous DMF was added DMAP (0.06 g, 0.5 mmol). The resulting mixture was stirred at room temperature for 12 h. The solvent was removed in vacuo to give a solid, which was recrystallized using ethyl acetate to produce 7 (1.72 g, 5.6 mmol) as a white solid in 56% yield: m.p.: 158-159° C.; IR (thin film): 3325, 1691, 1542, 1420, 1245, 1237 cm−1; 1H NMR (500 MHz, CDCl3): 6 1H NMR (500 MHz, CDCl3) δ 7.95-7.83 (m, 3H), 7.68 (d, J=8.2 Hz, 1H), 7.58-7.47 (m, 4H), 7.44-7.35 (m, 3H), 5.27 (s, 2H), 4.73 (d, J=5.8 Hz, 2H), 1.70 (t, J=6.0 Hz, 1H) ppm; 13C NMR (75 MHz, CDCl3): δ 154.43, 141.33, 140.53, 136.51, 135.70, 134.28, 132.55, 128.98, 128.90, 127.44, 127.41, 126.49, 126.24, 126.02, 125.35, 120.61, 67.25, 65.24 ppm. HRMS (m/z): [M+Na]+ calcd. for C19H17NNaO3, 330.1100; found, 330.1095. The solvent was removed in vacuo to give a solid, which was recrystallized

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

Procedure: To a solution of 1-isocyanatonaphthalene (1.69 g, 10 mmol) and 1,4-phenylene-dimethanol (4.14 g, 30 mmol) in anhydrous DMF was added DMAP (0.06 g, 0.5 mmol). The resulting mixture was stirred at room temperature for 12 h. The solvent was removed in vacuo to give a solid, which was recrystallized using ethyl acetate to produce 7 (1.72 g, 5.6 mmol) as a white solid in 56% yield: m.p.: 158-159° C.; IR (thin film): 3325, 1691, 1542, 1420, 1245, 1237 cm−1; 1H NMR (500 MHz, CDCl3): 6 1H NMR (500 MHz, CDCl3) δ 7.95-7.83 (m, 3H), 7.68 (d, J=8.2 Hz, 1H), 7.58-7.47 (m, 4H), 7.44-7.35 (m, 3H), 5.27 (s, 2H), 4.73 (d, J=5.8 Hz, 2H), 1.70 (t, J=6.0 Hz, 1H) ppm; 13C NMR (75 MHz, CDCl3): δ 154.43, 141.33, 140.53, 136.51, 135.70, 134.28, 132.55, 128.98, 128.90, 127.44, 127.41, 126.49, 126.24, 126.02, 125.35, 120.61, 67.25, 65.24 ppm. HRMS (m/z): [M+Na]+ calcd. for C19H17NNaO3, 330.1100; found, 330.1095. The solvent was removed in vacuo to give a solid, which was recrystallized

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

Procedure: In an analogous manner to that described in Example 1, from 4-(hydroxymethyl)benzyl alcohol and propargyl bromide there is obtained 4-[(2-propynyloxy)methyl]benzyl alcohol. This alcohol is reacted in an analogous manner to that described in Example 2 with cyclopropane carboxylic acid chloride to give cyclopropane carboxylic acid p-[(2-propynyloxy)methyl]benzyl ester.

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

Procedure: In an analogous manner to that described in Example 1, from 4-(hydroxymethyl)benzyl alcohol and propargyl bromide there is obtained 4-[(2-propynyloxy)methyl]benzyl alcohol. This alcohol is reacted in an analogous manner to that described in Example 2 with cyclopropane carboxylic acid chloride to give cyclopropane carboxylic acid p-[(2-propynyloxy)methyl]benzyl ester.

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

Procedure: Sodium hydride (0.17 g, 7.20 mmol) was added to a solution of 1,4-benzene dimethanol (1.00 g, 7.20 mmol) in THF at 0° C. The reaction was stirred for 1 h. 1-iodooctane (1.73 g; 7.20 mmol) was added and the reaction mixture was warmed to rt for 4 h and then heated at 50° C. for 2 days. The reaction was cooled and filtered. Silica gel chromatography eluting with 15% ethyl acetate/hexane gave 0.14 g of product: 1H NMR (500 MHz) δ 7.34-7.40 (m, 4H), 4.68-4.72 (m, 2H, 4.51 (s, 2H), 3.46-3.50 (m, 2H), 1.61-1.68 (m, 2H), 1.24-1.40 (m, 10H), 0.88-0.92 (m, 3H). heated at 50° C. for 2 days The reaction was cooled filtered Silica gel chromatography eluting with 15% ethyl acetate/hexane

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

Procedure: Sodium hydride (0.17 g, 7.20 mmol) was added to a solution of 1,4-benzene dimethanol (1.00 g, 7.20 mmol) in THF at 0° C. The reaction was stirred for 1 h. 1-iodooctane (1.73 g; 7.20 mmol) was added and the reaction mixture was warmed to rt for 4 h and then heated at 50° C. for 2 days. The reaction was cooled and filtered. Silica gel chromatography eluting with 15% ethyl acetate/hexane gave 0.14 g of product: 1H NMR (500 MHz) δ 7.34-7.40 (m, 4H), 4.68-4.72 (m, 2H, 4.51 (s, 2H), 3.46-3.50 (m, 2H), 1.61-1.68 (m, 2H), 1.24-1.40 (m, 10H), 0.88-0.92 (m, 3H). heated at 50° C. for 2 days The reaction was cooled filtered Silica gel chromatography eluting with 15% ethyl acetate/hexane

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

Procedure: A solution containing 1,4-benzenedimethanol (30 mmol), sodium hydride (25 mmol), catalytic amounts of tetrabutylammonium iodide, and 15-crown-5 (0.5 mmol) in tetrahyrofuran was stirred for 10 minutes. Cyclopropyl-4-fluorophenylketone (20 mmol) was added dropwise, and the solution was refluxed for 24 hours. The solvent was removed under reduced pressure. The residue was purified by column chromatography on silica gel (eluent: methylene chloride/methanol (98/2)). At 0° C. the product (4 mmol) was added to thionyl chloride (8 mmol). The temperature was raised to 70° C. for three hours. Excess thionyl chloride was evaporated and the residue purified by column chromatography on silica gel (eluent: methylene chloride/methanol (95/5)). The product (2 mmol), piperidine (4 mmol), catalytic amounts of potassium iodide, and potassium carbonate (6 mmol) dissolved in acetone were refluxed for 12 hours. The solvent was evaporated. The crude product was washed with water and extracted with ethyl acetate. The organic layer was removed under reduced pressure. The residue was crystallized with oxalic acid from diethyl ether/ethanol. the solution was refluxed for 24 hours The solvent was removed under reduced pressure The residue was purified by column chromatography on silica gel (eluent: methylene chloride/methanol (98/2)) Excess thionyl chloride was evaporated the residue purified by column chromatography on silica gel (eluent: methylene chloride/methanol (95/5)) were refluxed for 12 hours The solvent was evaporated The crude product was washed with water extracted with ethyl acetate The organic layer was removed under reduced pressure The residue was crystallized with oxalic acid from diethyl ether/ethanol

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

Procedure: A solution containing 1,4-benzenedimethanol (30 mmol), sodium hydride (25 mmol), catalytic amounts of tetrabutylammonium iodide, and 15-crown-5 (0.5 mmol) in tetrahyrofuran was stirred for 10 minutes. Cyclopropyl-4-fluorophenylketone (20 mmol) was added dropwise, and the solution was refluxed for 24 hours. The solvent was removed under reduced pressure. The residue was purified by column chromatography on silica gel (eluent: methylene chloride/methanol (98/2)). At 0° C. the product (4 mmol) was added to thionyl chloride (8 mmol). The temperature was raised to 70° C. for three hours. Excess thionyl chloride was evaporated and the residue purified by column chromatography on silica gel (eluent: methylene chloride/methanol (95/5)). The product (2 mmol), piperidine (4 mmol), catalytic amounts of potassium iodide, and potassium carbonate (6 mmol) dissolved in acetone were refluxed for 12 hours. The solvent was evaporated. The crude product was washed with water and extracted with ethyl acetate. The organic layer was removed under reduced pressure. The residue was crystallized with oxalic acid from diethyl ether/ethanol. the solution was refluxed for 24 hours The solvent was removed under reduced pressure The residue was purified by column chromatography on silica gel (eluent: methylene chloride/methanol (98/2)) Excess thionyl chloride was evaporated the residue purified by column chromatography on silica gel (eluent: methylene chloride/methanol (95/5)) were refluxed for 12 hours The solvent was evaporated The crude product was washed with water extracted with ethyl acetate The organic layer was removed under reduced pressure The residue was crystallized with oxalic acid from diethyl ether/ethanol

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

Procedure: To a mixture of sodium hydride (400 mg, 8.4 mmol, 50% in oil) and tetrahydrofuran (30 mL) was added 1,4-benzenedimethanol (2.3 g, 17 mmol) at 0° C., and then N,N-dimethylformamide (30 mL) was added. The reaction mixture was stirred at room temperature for 10 minutes, after which propargyl bromide (1.0 g, 8.4 mmol) was added dropwise to the reaction mixture at 0° C. The reaction mixture was stirred at room temperature for 1 hour, after which water was added to the reaction mixture, which was extracted with ethyl acetate. The organic layer was washed and saturated aqueous sodium chloride, and was concentrated under a reduced pressure. The residue thus obtained was purified by NH silica gel column chromatography (heptane:ethyl acetate=3:2) to obtain the title compound (860 mg, 58%). The reaction mixture was stirred at room temperature for 1 hour was extracted with ethyl acetate The organic layer was washed saturated aqueous sodium chloride, and was concentrated under a reduced pressure The residue thus obtained was purified by NH silica gel column chromatography (heptane:ethyl acetate=3:2)