反応 #1111863

反応方程式

2,6-Bis-(4-cyano phenoxy)-nicotinic acid

benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate

(2-piperidin-4-yl-ethyl)-carbamic acid tert-butyl ester

N,N-diisopropylethylamine

→

required product

(2-{1-[2,6-Bis-(4-cyano-phenoxy)-pyridine-3-carbonyl]-piperidin-4-yl}-ethyl)-carbamic Acid Tert-butyl Ester

溶媒

DMF

DMF

DMF

反応条件

後処理

1. 1
   温度was maintained below 5° C. during the addition
2. 2
   workup.STIRRINGThe mixture was stirred overnight at RT
3. 3
   濃縮The solvent was concentrated under reduced pressure
4. 4
   workup.DISSOLUTIONthe residue was dissolved in a mixture of water (150 ml) and ethyl acetate (150 ml)
5. 5
   その他the phases were separated
6. 6
   抽出The aqueous phase was extracted with ethyl acetate
7. 7
   洗浄The combined organic phase was washed with 10% solution of potassium hydrogen sulphate
8. 8
   乾燥and saturated brine solution, and dried over sodium sulphate
9. 9
   濃縮concentrated
10. 10
    その他The crude oily residue was purified by column chromatography

実験手順

A solution of 2,6-Bis-(4-cyano phenoxy)-nicotinic acid, 0.335 g (0.94 mmol), in 5 ml of DMF was added dropwise to the stirred suspension of 0.489 g (0.94 mmol) of benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate (PyBop) in 5 ml of DMF and followed by N,N-diisopropylethylamine 0.242 g (1.88 mmol) while the temperature was maintained below 5° C. during the addition. The mixture was stirred for 10 min and a solution of (2-piperidin-4-yl-ethyl)-carbamic acid tert-butyl ester (0.214 g, 0.94 mmol) in 2 ml of DMF was added. The mixture was stirred overnight at RT. The solvent was concentrated under reduced pressure and the residue was dissolved in a mixture of water (150 ml) and ethyl acetate (150 ml). The pH was adjusted to 2-3 with 6 N HCl and the phases were separated. The aqueous phase was extracted with ethyl acetate. The combined organic phase was washed with 10% solution of potassium hydrogen sulphate followed by saturated sodium bicarbonate solutiona and saturated brine solution, and dried over sodium sulphate and concentrated. The crude oily residue was purified by column chromatography using hexane-ethyl acetate (10:2) to afford 0.4 g of the required product. Percentage purity: 36.3%, (M+1)=567.2. 1H NMR (DMSO-d6): δ 1.35 (3H, m), 1.38 (9H, s), 1.65 (2H, m), 2.71 (2H, m), 2.95 (4H, m), 3.75 (2H, m), 6.80 (1H, t), 6.95 (1H, d), 7.32 (4H, d), 7.68 (1H, m), 7.85 (4H, d).

出典