Formic Acid → HCID 23001818, compound

Participants

Reaction Steps

Dicyclohexylcarbodiimide (460 mg, 2.23 mmol) was added to a solution of pentafluorophenol (413 mg, 2.24 mmol) in ether (10 mL) followed by formic acid (95 μL, 2.5 mmol). The mixture was stirred for 2 h and then filtered, washing the residue with ether. The filtrate was concentrated to ˜5 mL and a solution of the primary amine of Example 105 (411 mg, 1.1 mmol) in DCM (10 mL) was added. The mixture was stirred for 16 h then concentrated to an oily residue. This crude oil was taken up in a solution of BH3.THF in THF (1M, 20 mL, 20 mmol) and heated at reflux for 1.5 h under N2. After cooling to room temperature the reaction was quenched by the cautious addition of MeOH (10 mL) and then concentrated in vacuo. The oily residue was treated with 6M HCl and heated at reflux for 30 min. After cooling to room temperature the mixture was basified with aq K2CO3 and extracted with DCM (3×). The combined organic extracts were dried (MgSO4) and evaporated. The residue was purified by column chromatography [SiO2; 90:10:1 (DCM/MeOH/880 NH3)] to give a colourless oil which was taken up in EtOAc (20 mL) and treated with 1M ethereal HCl (2 mL). After stirring for 1.5 h the solid was collected by filtration to give the title product (282 mg, 60%); δH (CD3OD, 400 MHz) 2.78 (3H, s), 2.98 (3H, s), 3.18 (2H, m), 4.29 (2H, s), 4.39 (2H, m), 6.74 (1H, d), 6.80-6.90 (3H, m), 7.22 (1H, d), 7.44 (1H, s); MS m/z (TS+) 381 (MH+).

Provenance & Evidence