反应详情

温度

-78 °C

To a solution of 1-cyclopropyl-6-hydroxy-1H-indole-3-carbonitrile (0.59 g, 3.0 mmol) and triisopropylborate (1.03 mL, 4.5 mmol) in THF (15 mL) at −78° C. was added LDA (1.5M mono THF in cyclohexane, 4.60 mL, 6.9 mmol) with stirring. The mixture was stirred at −78° C. for 10 min and at room temperature for 30 min followed by the addition of (R)-(4-iodo-phenyl)-carbamic acid 1-cyclopropyl-ethyl ester (1.19 g, 3.6 mmol) and PdCl2 (dppf) (0.11 g, 0.15 mmol). The reaction mixture was cooled to −78° C. and flushed with nitrogen whereupon DMF (30 mL) and aq. K2CO3 (2.0M, 4.5 mL, 9.0 mmol) was added. The cooling bath was removed and the mixture was stirred overnight, poured into ice water (100 mL) and neutralized with acetic acid. The precipitate was filtered, washed with water, dried in air and purified on silica gel (CH2Cl2/EtOAc, 9:1) to give (R)-[4-(3-cyano-1-cyclopropyl-6-hydroxy-1H-indol-2-yl)-phenyl]-carbamic acid 1-cyclopropyl-ethyl ester as a solid (1.16 g, 97%).

1. stirringThe mixture was stirred at −78° C. for 10 min and at room temperature for 30 min
2. additionwas added
3. customThe cooling bath was removed
4. stirringthe mixture was stirred overnight
5. additionpoured into ice water (100 mL)
6. filtrationThe precipitate was filtered
7. washwashed with water
8. customdried in air
9. custompurified on silica gel (CH2Cl2/EtOAc, 9:1)