Trimethylsilyldiazomethane → Methyl 5-(hydroxymethyl) furan-2-carboxylate

Participants

Reaction Steps

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).

Provenance & Evidence