反应详情

The solution of (4-methyl-pyridin-2-yl)-carbamic acid tert-butyl ester (200 mg, 0.96 mmol) in dry THF (10 mL) is cooled to −78° C. The 1.6 M n-BuLi in hexane solution (3.0 mL, 4.8 mmol) is added dropwise at −78° C. Then the cooling bath is removed and the mixture is stirred at room temperature for 15 min. The reaction mixture is cooled down to −78° C. again and 4-methylbenzylaldehyde (231 mg, 1.9 mmol) is added. The mixture is stirred for another 30 min at −78° C. and saturated NH4Cl aquaous solution (25 mL) is added. The reaction mixture is then warmed up to room temperature and EtOAc (30 mL) is added along with water (30 mL). The resulting mixture is stirred for 10 min and the aqueous layer is separated and extracted with EtOAc (3×35 ml). The combined organic layers are washed with brine, dried over anhydrous sodium sulfate and concentrated. The crude is purified by silica flash column chromatography eluting with EtOAc in Heptane (gradient from 0% to 60%) to give 80 mg of the desired product.

1. customThen the cooling bath is removed
2. temperatureThe reaction mixture is cooled down to −78° C. again
3. stirringThe mixture is stirred for another 30 min at −78° C.
4. temperatureThe reaction mixture is then warmed up to room temperature
5. stirringThe resulting mixture is stirred for 10 min
6. customthe aqueous layer is separated
7. extractionextracted with EtOAc (3×35 ml)
8. washThe combined organic layers are washed with brine
9. dry with materialdried over anhydrous sodium sulfate
10. concentrationconcentrated
11. customThe crude is purified by silica flash column chromatography
12. washeluting with EtOAc in Heptane (gradient from 0% to 60%)