Hydrochloric Acid → HCID 178429017, compound

Participants

Reaction Conditions

Reaction Steps

(2-aminophenyl)methanol (4000 mg, 32.48 mmol) was dissolved in water (25 mL) with concentrated HCl (6 N, 7.00 mL, 42.2 mmol) and the solution was cooled in an ice/NaCl bath to −5° C., afterward sodium nitrite (2420 mg, 39 mmol) in 20 mL of water was added dropwise over 20 minutes. Solids precipitated out. The organic mixture/suspension was stirred at −5° C.→0° C. for 25 minutes. 5 mL CH3CN was added. The solution of 3,5-dimethylphenol (3970 mg, 32.5 mmol) in CH3CN (10 mL) was mixed with a solution of Na2CO3 (13.8 g, 130 mmol) in H2O (20 mL). The mixed solution was added to the above diazonium solution slowly at −5° C.→0° C. The mixture was stirred at −5° C.→0° C. for 2 hours. Brownish solids precipitated out. The mixture was neutralized with conc. HCl (12 N) and diluted with EtOAc. The suspension filtered through celite and washed with EtOAc which was used for extraction. After four extractions, the combine dark brownish organic layers were washed with brine, dried over Na2SO4 and concentrated, leading to dark brownish solids. The crude was dissolved in EtOAc and loaded to the column and purified by ISCO (120 g silica gel, EtOAc/Heptane: 0→45%), leading the desired product as orange solids. 1H NMR (400 MHz, DMSO-d6) δ ppm 2.42 (s, 6H) 4.96 (d, J=5.66 Hz, 2H) 5.14-5.25 (m, 1H) 6.58 (s, 2H) 7.29-7.36 (m, 1H) 7.41-7.50 (m, 2H) 7.65 (d, J=0.78 Hz, 1H) 9.92 (s, 1H). LCMS: m/z=257.3 [M+H].

Provenance & Evidence