Hydrochloric Acid → Methyl 5-fluoro-3-benzofurancarboxylate
Reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]2[O:9][CH:8]=[C:7]([C:10]([OH:12])=[O:11])[C:6]=2[CH:13]=1.Cl.[CH3:15]O>>[F:1][C:2]1[CH:3]=[CH:4][C:5]2[O:9][CH:8]=[C:7]([C:10]([O:12][CH3:15])=[O:11])[C:6]=2[CH:13]=1Participants
Procedure
A solution of 5-fluorobenzofuran-3-carboxylic acid (56 g) and saturated etheral solution of hydrochloric gas (300 mL) in methanol (600 mL) was stirred for 16 h at room temperature. Further etheral HCl was added (300 mL) followed by stirring for 24 h. Concentration in vacuo gave a dark crystalline material, methyl 5-fluorobenzofuran-3-carboxylate (58 g). Lithium aluminium hydride (15 g) was suspended in tetrahydrofuran (400 mL) under a nitrogen atmosphere followed by dropwise addition of a solution of methyl 5-fluorobenzofuran-3-carboxylate (58 g) in tetrahydrofuran (300 mL). The temperature increased to 55° C. during the addition. After stirring for 2 h the reaction was quenched successively with water (30 mL), 15% aq. sodium hydroxide (15 mL), and water (75 mL). Further tetrahydrofuran (500 mL) was added and the mixture stirred for 1 h. The mixture was filtered and the precipitate extracted with a mixture of methylene chloride (1 L) and ethanol (0.5 L). The combined organic phases were concentrated in vacuo giving an oil which was applied to silica gel flash chromatography (eluent: methylene chloride/25% aq. NH3 99:1). The resulting yellow oil, 5-fluorobenzofuran-3-ylmethanol (14.4 g) crystallised on standing.
Workup
- concentrationConcentration in vacuo
Sources & evidence
- ORD record
- ord-c0f7d1a8226045a68884a7e6d81d2193
- Source dataset
- uspto-grants-2003_07
- Patent number
- US06596722B2
Reaction notes
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