反应详情

2-(3-tert-Butylphenyl)-1-(methoxycarbonyl)piperidine-4-carboxylic acid (2.73 g, 8.55 mmol) (reference compound 14) was dissolved in methyl THF (40 mL) and di(1H-imidazol-1-yl)methanone (2.079 g, 12.82 mmol) added. The suspension was stirred at room temperature under nitrogen for 2 h (flask 1). In a separate flask potassium 3-ethoxy-3-oxopropanoate (2.62 g, 15.39 mmol) was suspended in methyl THF (60 mL) and magnesium chloride (1.465 g, 15.39 mmol) added. The suspension was stirred at 50° C. under nitrogen for 3 h using an oversized stirring bar (flask 2). The beige suspension in flask 1 was now added to the white suspension in flask 2. The resulting beige suspension was stirred under nitrogen at room temperature for 23 h. The mixture was acidified to pH 1 with 0.5 M HCl (100 mL) and MTBE (200 mL) was added. The phases were separated and the organic phase extracted with water (30 mL), satd NaHCO3 (30 mL) and water (30 mL), dried over anhydrous Na2SO4, and evaporated to yield crude methyl 2-(3-tert-butylphenyl)-4-(3-ethoxy-3-oxopropanoyl)-piperidine-1-carboxylate (3.14 g, 95%) as a brown oil.

1. stirringThe suspension was stirred at 50° C. under nitrogen for 3 h
2. additionThe beige suspension in flask 1 was now added to the white suspension in flask 2
3. stirringThe resulting beige suspension was stirred under nitrogen at room temperature for 23 h
4. additionwas added
5. customThe phases were separated
6. extractionthe organic phase extracted with water (30 mL), satd NaHCO3 (30 mL) and water (30 mL)
7. dry with materialdried over anhydrous Na2SO4
8. customevaporated