3,5-bis(hydroxymethyl)benzonitrile

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: Hydrogen chloride gas was passed through a solution of 3,5-bis-hydroxymethyl-benzonitrile (50 mg, 0.23 mmol) in anhydrous ethanol (100 mL) at room temperature. After 5 h, hydrogen chloride gas was stopped. The solvent was evaporated in vacuo and the residue was triturated in diethyl ether to afford ethyl 3,5-bis-hydroxymethyl-benzimidate hydrochloride (52 mg, 92%). It was used without further purification. The solvent was evaporated in vacuo the residue was triturated in diethyl ether

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

Procedure: To a solution of 3,5-bis-(tert-butyl-dimethyl-silanyloxymethyl)-benzonitrile (1.45 g, 3.702 mmol) in tetrahydrofuran (30 mL) at room temperature was added tetrabutylammonium fluoride (9.255 mL, 9.255 mmol, 1 M in tetrahydrofuran). The reaction mixture was stirred at room temperature for 2 h then concentrated in vacuo. The residue was partitioned between ethyl acetate (20 mL) and water (30 mL). The layers were separated and the product was extracted with ethyl acetate (3×20 mL). The organic layers were washed with brine and dried over anhydrous magnesium sulfate. The solid was filtered off, and the filtrate was concentrated in vacuo. Purification of the residue by flash chromatography (Biotage system, KP-Sil™ 32-63 μm, 60 Å silica gel) eluting with 75% ethyl acetate in hexanes yielded 3,5-bis-hydroxymethyl-benzonitrile (465 mg, 77%). then concentrated in vacuo The residue was partitioned between ethyl acetate (20 mL) and water (30 mL) The layers were separated the product was extracted with ethyl acetate (3×20 mL) The organic layers were washed with brine dried over anhydrous magnesium sulfate The solid was filtered off the filtrate was concentrated in vacuo Purification of the residue by flash chromatography (Biotage system, KP-Sil™ 32-63 μm, 60 Å silica gel) eluting with 75% ethyl acetate in hexanes