反应详情

A solution of chloroacetyl chloride (0.71 mL, 8.94 mmol) in THF (5 mL) was added dropwise to a solution/suspension of 2-amino-6-methylphenol (1 g, 8.13 mmol) and triethylamine (1.24 mL, 8.94 mmol) in THF (50 mL) which had been pre-cooled in an ice-water bath. After stirring for 5 minutes a further portion of triethylamine (1.24 mL, 8.94 mmol) was added. The mixture was stirred and warmed to r. t. After 24 h the reaction was allowed to stand overnight. The mixture was concentrated in vacuo and the residue was partitioned between water (100 mL) and EtOAc (50 mL). Brine (20 mL) was added to the aqueous phase, and this was further extracted with EtOAc (50 mL). The combined organic fractions were dried (MgSO4), concentrated in vacuo, and purified by column chromatography (SiO2, 20-100% EtOAc/heptane) to give an orange-brown solid (1.04 g), which was dissolved in THF (10 mL) and triethylamine (2 mL), and the mixture left to stand for 3 days. The mixture was concentrated in vacuo and purified by column chromatography (SiO2, 10-50% EtOAc/heptane) to give a cream solid (0.6 g). This was dissolved in DCM (40 mL), and the solution was washed with aqueous NaOH (2M, 10 mL). The organic fraction was dried (MgSO4) and concentrated in vacuo to give the title compound (0.29 g, 22%) as a beige solid. LCMS (ES+) 164 (M+H)+, RT 2.61 minutes (Method 1).

1. temperaturehad been pre-cooled in an ice-water bath
2. additionwas added
3. temperaturewarmed to r
4. waitto stand overnight
5. concentrationThe mixture was concentrated in vacuo
6. customthe residue was partitioned between water (100 mL) and EtOAc (50 mL)
7. additionBrine (20 mL) was added to the aqueous phase
8. extractionthis was further extracted with EtOAc (50 mL)
9. dry with materialThe combined organic fractions were dried (MgSO4)
10. concentrationconcentrated in vacuo
11. custompurified by column chromatography (SiO2, 20-100% EtOAc/heptane)