[5-(hydroxymethyl)furan-2-yl]methanol

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

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

Procedure: According to the method of P. G. McDougal, et al., J. Org. Chem., 5, 3388-3390 (1986), combine hexane washed sodium hydride (20 mmol) and tetrahydrofuran (40 mL). Slowly add 2,5-furandimethanol (20 mmol). After gas evolution ceases, add t-butyldimethylsilyl chloride (20 mmol) and stir vigorously. After about 1 hour, pour the reaction mixture into diethyl ether and extract with a saturated aqueous solution of sodium carbonate, water, and then brine. Dry the organic layer over Na2SO4, filter, and evaporate in vacuo to give 5-(t-butyldimethylsilyloxy)methyl-2-hydroxymethylfuran. Combine 1-(t-butoxycarbonyl)-4-(1H-benzimidazole-2-carbonyl)piperidine (10 mmol), 5-(t-butyldimethylsilyloxy)-methyl-2-hydroxymethylfuran (10 mmol), and triphenylphosphine (10 mmol) in tetrahydrofuran (100 mL). Add diethyl azodicarboxylate (10 mmol). After 18 hours, evaporate the reaction mixture in vacuo to give a residue. Partition the residue between ethyl acetate and water. Separate the organic layer and extract with water and brine. Dry the organic layer over Na2SO4, filter, and evaporate in vacuo to give a residue. Chromatograph the residue on silica gel to give 1-(t-butoxycarbonyl)-4-(1-(5-(t-butyldimethylsilyloxy)-methylfur-2-ylmethyl)-1H-benzimidazole-2-carbonyl)piperidine. extract with a saturated aqueous solution of sodium carbonate, water Dry the organic layer over Na2SO4 filter evaporate in vacuo

Conditions: temp:-40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of furan-2,5-dimethanol (25 mg, 0.2 mol) and pyridine (38.4 g, 0.48 mol) in a dry chloroform (120 mL) was added dropwise a solution of thionyl chloride (52.4 g, 0.44 mol) in dry chloroform (80 mL) at -40° C. (Ar) for 1.5 h. After addition, the mixture was stirred at -40° C. for 0.5 h then warmed to 0° C. for 0.5 h. After quenching with ice water (300 mL), the organic phase was washed with 5% sodium hydroxide (10 mL), dried, then evaporated to give a light brown oil. The brownish oil was distilled under vacuum (80°-82° C., 0.5 mmHg) to give a colorless liquid which solidified at room temperature. Yield: 24 g (75%); M.P. 27°-28° C. (M.P. 27°-28° C., K. Yu. Noritskii, V. P. Volkoo, and Yu. K. Yuiey, Zhur. Obscher. Khim., 1961, 31, 538.) After addition then warmed to 0° C. for 0.5 h After quenching with ice water (300 mL) the organic phase was washed with 5% sodium hydroxide (10 mL) dried evaporated to give a light brown oil The brownish oil was distilled under vacuum (80°-82° C., 0.5 mmHg) to give a colorless liquid which solidified at room temperature

Conditions: temp:-40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of furan-2,5-dimethanol (25 mg, 0.2 mol) and pyridine (38.4 g, 0.48 mol) in a dry chloroform (120 mL) was added dropwise a solution of thionyl chloride (52.4 g, 0.44 mol) in dry chloroform (80 mL) at -40° C. (Ar) for 1.5 h. After addition, the mixture was stirred at -40° C. for 0.5 h then warmed to 0° C. for 0.5 h. After quenching with ice water (300 mL), the organic phase was washed with 5% sodium hydroxide (10 mL), dried, then evaporated to give a light brown oil. The brownish oil was distilled under vacuum (80°-82° C., 0.5 mmHg) to give a colorless liquid which solidified at room temperature. Yield 24 g (75%); M.P. 27°-28° C. (M.P. 27°-28° C., K. Yu. Noritskii, V. P. Volkoo, and Yu. K. Yuiey, Zhur. Obscher. Khim., 1961, 31, 538.) After addition then warmed to 0° C. for 0.5 h After quenching with ice water (300 mL) the organic phase was washed with 5% sodium hydroxide (10 mL) dried evaporated to give a light brown oil The brownish oil was distilled under vacuum (80°-82° C., 0.5 mmHg) to give a colorless liquid which solidified at room temperature

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

Procedure: According to the method of P. G. McDougal, et al., J. Org. Chem., 51, 3388-3390 (1986), combine hexane washed sodium hydride (20 mmol) and tetrahydrofuran (40 mL). Slowly add 2,5-furandimethanol (20 mmol). After gas evolution ceases, add t-butyldimethylsilyl chloride (20 mmol) and stir vigorously. After about 1 hour, pour the reaction mixture into diethyl ether and extract with a saturated aqueous solution of sodium carbonate, water, and then brine. Dry the organic layer over Na2SO4, filter, and evaporate in vacuo to give 5-(t-butyldimethylsilyloxy)methyl-2-hydroxymethylfuran. Combine 1-(t-butoxycarbonyl)-4-(1H-benzimidazole-2-carbonyl)piperidine (10 mmol), 5-(t-butyldimethylsilyloxy)-methyl-2-hydroxymethylfuran (10 mmol), and triphenylphosphine (10 mmol) in tetrahydrofuran (100 mL). Add diethyl azodicarboxylate (10 mmol). After 18 hours, evaporate the reaction mixture in vacuo to give a residue. Partition the residue between ethyl acetate and water. Separate the organic layer and extract with water and brine. Dry the organic layer over Na2SO4, filter, and evaporate in vacuo to give a residue. Chromatograph the residue on silica gel to give 1-(t-butoxycarbonyl)-4-(1-(5-(t-butyldimethylsilyloxy)-methylfur-2-ylmethyl)-1H-benzimidazole-2-carbonyl)piperidine. extract with a saturated aqueous solution of sodium carbonate, water Dry the organic layer over Na2SO4 filter evaporate in vacuo

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

Procedure: According to the method of P. G. McDougal, et al., J. Org. Chem., 51, 3388-3390 (1986), combine hexane washed sodium hydride (20 mmol) and tetrahydrofuran (40 mL). Slowly add 2,5-furandimethanol (20 mmol). After gas evolution ceases, add t-butyldimethylsilyl chloride (20 mmol) and stir vigorously. After about 1 hour, pour the reaction mixture into diethyl ether and extract with a saturated aqueous solution of sodium carbonate, water, and then brine. Dry the organic layer over Na2SO4, filter, and evaporate in vacuo to give 5-(t-butyldimethylsilyloxy)methyl-2-hydroxymethylfuran. Combine 1-(t-butoxycarbonyl)-4-(1H-benzimidazole-2-carbonyl)piperidine (10 mmol), 5-(t-butyldimethylsilyloxy)-methyl-2-hydroxymethylfuran (10 mmol), and triphenylphosphine (10 mmol) in tetrahydrofuran (100 mL). Add diethyl azodicarboxylate (10 mmol). After 18 hours, evaporate the reaction mixture in vacuo to give a residue. Partition the residue between ethyl acetate and water. Separate the organic layer and extract with water and brine. Dry the organic layer over Na2SO4, filter, and evaporate in vacuo to give a residue. Chromatograph the residue on silica gel to give 1-(t-butoxycarbonyl)-4-(1-(5-(t-butyldimethylsilyloxy)-methylfur-2-ylmethyl)-1H-benzimidazole-2-carbonyl)piperidine. extract with a saturated aqueous solution of sodium carbonate, water Dry the organic layer over Na2SO4 filter evaporate in vacuo

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

Procedure: According to the method of P. G. McDougal, et al., J. Org. Chem., 5, 3388-3390 (1986), combine hexane washed sodium hydride (20 mmol) and tetrahydrofuran (40 mL). Slowly add 2,5-furandimethanol (20 mmol). After gas evolution ceases, add t-butyldimethylsilyl chloride (20 mmol) and stir vigorously. After about 1 hour, pour the reaction mixture into diethyl ether and extract with a saturated aqueous solution of sodium carbonate, water, and then brine. Dry the organic layer over Na2SO4, filter, and evaporate in vacuo to give 5-(t-butyldimethylsilyloxy)methyl-2-hydroxymethylfuran. Combine 1-(t-butoxycarbonyl)-4-(1H-benzimidazole-2-carbonyl)piperidine (10 mmol), 5-(t-butyldimethylsilyloxy)-methyl-2-hydroxymethylfuran (10 mmol), and triphenylphosphine (10 mmol) in tetrahydrofuran (100 mL). Add diethyl azodicarboxylate (10 mmol). After 18 hours, evaporate the reaction mixture in vacuo to give a residue. Partition the residue between ethyl acetate and water. Separate the organic layer and extract with water and brine. Dry the organic layer over Na2SO4, filter, and evaporate in vacuo to give a residue. Chromatograph the residue on silica gel to give 1-(t-butoxycarbonyl)-4-(1-(5-(t-butyldimethylsilyloxy)-methylfur-2-ylmethyl)-1H-benzimidazole-2-carbonyl)piperidine. extract with a saturated aqueous solution of sodium carbonate, water Dry the organic layer over Na2SO4 filter evaporate in vacuo

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

Procedure: According to the method of P. G. McDougal, et al., J. Org. Chem., 5, 3388-3390 (1986), combine hexane washed sodium hydride (20 mmol) and tetrahydrofuran (40 mL). Slowly add 2,5-furandimethanol (20 mmol). After gas evolution ceases, add t-butyldimethylsilyl chloride (20 mmol) and stir vigorously. After about 1 hour, pour the reaction mixture into diethyl ether and extract with a saturated aqueous solution of sodium carbonate, water, and then brine. Dry the organic layer over Na2SO4, filter, and evaporate in vacuo to give 5-(t-butyldimethylsilyloxy)methyl-2-hydroxymethylfuran. Combine 1-(t-butoxycarbonyl)-4-(1H-benzimidazole-2-carbonyl)piperidine (10 mmol), 5-(t-butyldimethylsilyloxy)-methyl-2-hydroxymethylfuran (10 mmol), and triphenylphosphine (10 mmol) in tetrahydrofuran (100 mL). Add diethyl azodicarboxylate (10 mmol). After 18 hours, evaporate the reaction mixture in vacuo to give a residue. Partition the residue between ethyl acetate and water. Separate the organic layer and extract with water and brine. Dry the organic layer over Na2SO4, filter, and evaporate in vacuo to give a residue. Chromatograph the residue on silica gel to give 1-(t-butoxycarbonyl)-4-(1-(5-(t-butyldimethylsilyloxy)-methylfur-2-ylmethyl)-1H-benzimidazole-2-carbonyl)piperidine. extract with a saturated aqueous solution of sodium carbonate, water Dry the organic layer over Na2SO4 filter evaporate in vacuo

Conditions: temp:-40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of furan-2,5-dimethanol (25 mg, 0.2 mol) and pyridine (38.4 g, 0.48 mol) in a dry chloroform (120 mL) was added dropwise a solution of thionyl chloride (52.4 g, 0.44 mol) in dry chloroform (80 mL) at -40° C. (Ar) for 1.5 h. After addition, the mixture was stirred at -40° C. for 0.5 h then warmed to 0° C. for 0.5 h. After quenching with ice water (300 mL), the organic phase was washed with 5% sodium hydroxide (10 mL), dried, then evaporated to give a light brown oil. The brownish oil was distilled under vacuum (80°-82° C., 0.5 mmHg) to give a colorless liquid which solidified at room temperature. Yield: 24 g (75%); M.P. 27°-28° C. (M.P. 27°-28° C., K. Yu. Noritskii, V. P. Volkoo, and Yu. K. Yuiey, Zhur. Obscher. Khim., 1961, 31, 538.) After addition then warmed to 0° C. for 0.5 h After quenching with ice water (300 mL) the organic phase was washed with 5% sodium hydroxide (10 mL) dried evaporated to give a light brown oil The brownish oil was distilled under vacuum (80°-82° C., 0.5 mmHg) to give a colorless liquid which solidified at room temperature

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

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

Procedure: Prepare by the method of Example 84.1 using 1-(3,4,5-trimethoxy-benzoyl)-3-[2-[4-[1H-benzoimidazole-2-carbonyl]-piperidin-1-yl]-ethyl]-3-phenyl-pyrrolidine (1 mmol) and 2,5-di(hydroxymethyl)furan (10 mmol) to give the title compound.

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

Procedure: In another aspect, the present disclosure provides a method C for preparing 2,5-dimethylfuran, which includes the steps of: a) combining 5-(hydroxymethyl)furfural (HMF) with H2, a first catalyst, and an aprotic solvent; b) reacting the mixture of step (a) to form 2,5-bis(hydroxymethyl)furan (BHMF); c) adding a carboxylic acid, and a second catalyst to the reaction mixture of step (b) to form an ester of BHMF; and d) adding H2 to the reaction mixture that includes the ester of BHMF of step (c) to form 2,5-dimethylfuran. In another aspect, the present disclosure provides a method C