methyl 5-(hydroxymethyl)furan-2-carboxylate

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

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

Procedure: Methyl 5-(hydroxymethyl)-furan-2-carboxylate was synthesized according to procedure described in Raimundo, B. C., et al., J. Med. Chem., 2004, 47 (12), 3111-3130). 5-formyl-2-furan carboxylic acid (1 g, 7.14 mmoles) was stirred in benzene (18 mL)/methanol (4 mL) in a 3-neck 50 mL round bottom flask with one neck connected to a funnel that was previously flushed with nitrogen gas. Trimethylsilyl diazomethane 2M in hexanes (3.6 mL, 7.2 mmoles) was added dropwise over a period of 15 min. After addition, the medium was a green limpid solution, which was stirred for 2 h at room temperature. The reaction advancement is monitored by TLC 8:2 Hexanes/AcOEt followed by 95:5 CHCl3/MeOH, and stained with KMnO4. Solvents were evaporated under vacuum, and 14 mL of methanol was added. The flask was placed in an ice-water bath and sodium borohydride (600 mg, 15.8 mmoles) was added. The reaction mixture was stirred for 3 h at room temperature. Water was poured off and the mixture extracted with AcOEt. The organic phase was dried over MgSO4, and the solvent was evaporated. The product was purified by silica gel column chromatography (7×3.5 cm) with 100 mL of 90:10, then 200 mL of 80:20, and finally 400 mL of a 75:25 mixture of Hexane/AcOEt to yield a yellow powder after extraction (780 mg, 70%). NMR 1H 300 MHz, CDCl3, (δ, ppm): 7.13 (d, J=3.4 Hz, 1H), 6.41 (d, J=3.3 Hz, 1H), 4.67 (d, J=6.2 Hz, 2H), 3.89 (s, 3H). connected to a funnel that was previously flushed with nitrogen gas After addition Solvents were evaporated under vacuum, and 14 mL of methanol was added The flask was placed in an ice-water bath The reaction mixture was stirred for 3 h at room temperature the mixture extracted with AcOEt The organic phase was dried over MgSO4 the solvent was evaporated The product was purified by silica gel column chromatography (7×3.5 cm) with 100 mL of 90:10 200 mL of 80:20, and finally 400 mL of a 75:25 mixture of Hexane/AcOEt to yield a yellow powder after extraction (780 mg, 70%)

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

Procedure: Methyl 5-(hydroxymethyl)-furan-2-carboxylate was synthesized according to procedure described in Raimundo, B. C., et al., J. Med. Chem., 2004, 47 (12), 3111-3130). 5-formyl-2-furan carboxylic acid (1 g, 7.14 mmoles) was stirred in benzene (18 mL)/methanol (4 mL) in a 3-neck 50 mL round bottom flask with one neck connected to a funnel that was previously flushed with nitrogen gas. Trimethylsilyl diazomethane 2M in hexanes (3.6 mL, 7.2 mmoles) was added dropwise over a period of 15 min. After addition, the medium was a green limpid solution, which was stirred for 2 h at room temperature. The reaction advancement is monitored by TLC 8:2 Hexanes/AcOEt followed by 95:5 CHCl3/MeOH, and stained with KMnO4. Solvents were evaporated under vacuum, and 14 mL of methanol was added. The flask was placed in an ice-water bath and sodium borohydride (600 mg, 15.8 mmoles) was added. The reaction mixture was stirred for 3 h at room temperature. Water was poured off and the mixture extracted with AcOEt. The organic phase was dried over MgSO4, and the solvent was evaporated. The product was purified by silica gel column chromatography (7×3.5 cm) with 100 mL of 90:10, then 200 mL of 80:20, and finally 400 mL of a 75:25 mixture of Hexane/AcOEt to yield a yellow powder after extraction (780 mg, 70%). NMR 1H 300 MHz, CDCl3, (δ, ppm): 7.13 (d, J=3.4 Hz, 1H), 6.41 (d, J=3.3 Hz, 1H), 4.67 (d, J=6.2 Hz, 2H), 3.89 (s, 3H). connected to a funnel that was previously flushed with nitrogen gas After addition Solvents were evaporated under vacuum, and 14 mL of methanol was added The flask was placed in an ice-water bath The reaction mixture was stirred for 3 h at room temperature the mixture extracted with AcOEt The organic phase was dried over MgSO4 the solvent was evaporated The product was purified by silica gel column chromatography (7×3.5 cm) with 100 mL of 90:10 200 mL of 80:20, and finally 400 mL of a 75:25 mixture of Hexane/AcOEt to yield a yellow powder after extraction (780 mg, 70%)

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

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

Procedure: A solution of 5-formyl-2-furancarboxylic acid methyl ester in 65 ml of tetrahydrofuran was treated with 14 ml of a 3M solution of methyl magnesium bromide in ether at 0°-5° C. The reaction mixture was stirred at the same temperature for 1 hour, poured into a saturated solution of ammonium chloride and extracted with ether. The organic phase was washed with water, dried over anhydrous magnesium sulfate and concentrated giving 6.3 g (87.8%) of 5-(1-hydroxymethyl)-2-furan carboxylic acid methyl ester as a pale yellow oil after chromatographic purification. The oxidation of this secondary alcohol was carried out by using the Swern oxidation conditions. Thus, 6.3 g of 5-(1-hydroxy- methyl) -2-furancarboxylic acid methyl ester in 60 ml of methylene chloride was added to a stirred solution of 5 g of oxalyl chloride, 7.1 g of dimethyl sulfoxide in 80 ml of methylene chloride at -60° C. The reaction mixture was stirred 15 minutes at the same temperature, then 17.5 ml of triethylamine was added. The cooling bath was removed allowing the temperature to rise to 25° C. The reaction mixture was then treated with 25 ml of water, stirred for 10 minutes and extracted with methylene chloride. The organic phase was washed with water, dried over anhydrous magnesium sulfate and concentrated in vacuo to give 6.7 g of a brown oil. Chromatographic purification of this material on a silica gel column followed by crystallization from ethyl acetate-hexane gave 3.5 g (56.2%) of 5-acetyl-2-furancarboxylic acid methyl ester as a white solid, mp 101°-102° C. extracted with ether The organic phase was washed with water dried over anhydrous magnesium sulfate concentrated

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

Procedure: 5-formyl-2-furan carboxylic acid (1 g, 7.14 mmoles) was stirred in benzene (18 mL)/methanol (4 mL) in a 3-neck 50 mL round bottom flask with one neck connected to a funnel that was previously flushed with nitrogen gas. Trimethylsilyl diazomethane 2M in hexanes (3.6 mL, 7.2 mmoles) was added dropwise over a period of 15 min. After addition, the medium was a green limpid solution, which was stirred for 2 h at r.t. The reaction advancement is monitored by TLC 8:2 Hexanes/AcOEt followed by 95:5 CHCl3/MeOH, and stained with KMnO4. Solvents were evaporated under vacuum, and 14 mL of methanol was added. The flask was placed in an ice-water bath and sodium borohydride (600 mg, 15.8 mmoles) was added. The reaction mixture was stirred for 3 h at r.t. Water was poured off and the mixture extracted with AcOEt. The organic phase was dried over MgSO4, and the solvent was evaporated. The product was purified by silica gel column chromatography (7×3.5 cm) with 100 mL of 90:10, then 200 mL of 80:20, and finally 400 mL of a 75:25 mixture of Hexane/AcOEt to yield a yellow powder after extraction (780 mg, 70%). NMR 1H 300 MHz, CDCl3, (δ, ppm): 7.13 (d, J=3.4 Hz, 1H), 6.41 (d, J=3.3 Hz, 1H), 4.67 (d, J=6.2 Hz, 2H), 3.89 (s, 3H). connected to a funnel that was previously flushed with nitrogen gas After addition Solvents were evaporated under vacuum, and 14 mL of methanol was added The flask was placed in an ice-water bath The reaction mixture was stirred for 3 h at r.t the mixture extracted with AcOEt The organic phase was dried over MgSO4 the solvent was evaporated The product was purified by silica gel column chromatography (7×3.5 cm) with 100 mL of 90:10 200 mL of 80:20, and finally 400 mL of a 75:25 mixture of Hexane/AcOEt to yield a yellow powder after extraction (780 mg, 70%)

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

Procedure: Methyl 5-(hydroxymethyl)-furan-2-carboxylate was synthesized according to procedure described in Raimundo, B. C., et al., J. Med. Chem., 2004, 47 (12), 3111-3130). 5-formyl-2-furan carboxylic acid (1 g, 7.14 mmoles) was stirred in benzene (18 mL)/methanol (4 mL) in a 3-neck 50 mL round bottom flask with one neck connected to a funnel that was previously flushed with nitrogen gas. Trimethylsilyl diazomethane 2M in hexanes (3.6 mL, 7.2 mmoles) was added dropwise over a period of 15 min. After addition, the medium was a green limpid solution, which was stirred for 2 h at room temperature. The reaction advancement is monitored by TLC 8:2 Hexanes/AcOEt followed by 95:5 CHCl3/MeOH, and stained with KMnO4. Solvents were evaporated under vacuum, and 14 mL of methanol was added. The flask was placed in an ice-water bath and sodium borohydride (600 mg, 15.8 mmoles) was added. The reaction mixture was stirred for 3 h at room temperature. Water was poured off and the mixture extracted with AcOEt. The organic phase was dried over MgSO4, and the solvent was evaporated. The product was purified by silica gel column chromatography (7×3.5 cm) with 100 mL of 90:10, then 200 mL of 80:20, and finally 400 mL of a 75:25 mixture of Hexane/AcOEt to yield a yellow powder after extraction (780 mg, 70%). NMR 1H 300 MHz, CDCl3, (δ, ppm): 7.13 (d, J=3.4 Hz, 1H), 6.41 (d, J=3.3 Hz, 1H), 4.67 (d, J=6.2 Hz, 2H), 3.89 (s, 3H). connected to a funnel that was previously flushed with nitrogen gas After addition Solvents were evaporated under vacuum, and 14 mL of methanol was added The flask was placed in an ice-water bath The reaction mixture was stirred for 3 h at room temperature the mixture extracted with AcOEt The organic phase was dried over MgSO4 the solvent was evaporated The product was purified by silica gel column chromatography (7×3.5 cm) with 100 mL of 90:10 200 mL of 80:20, and finally 400 mL of a 75:25 mixture of Hexane/AcOEt to yield a yellow powder after extraction (780 mg, 70%)