反应详情

A suspension of (3-methoxy-4-nitrobenzyl)prop-2-en-1-ylphosphinic acid (Compound 37E, 241 mg, 0.888 mmol) and 3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]propan-1-ol (Compound 3E, 224 mg, 0.888 mmol) in 1,2-Dichloroethane (19 mL) and DIPEA (0.928 mL, 5.33 mmol) was charged with (benzotriazol-1-yloxy)tripyrrolidino-phosphonium hexafluorophosphate (1387 mg, 2.665 mmol). The reaction mixture was stirred at rt for 16 hours. The reaction mixture was quenched with water (10 mL) and extracted with DCM (20 mL). The organic layer was washed with NaHCO3 (10 mL), washed with brine (15 mL), dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to a yellow oil. The crude material was purified on a Teledyne ISCO Combiflash® Rf system using DCM/MeOH (100:0→95:5) as eluent. The fractions containing product were combined and concentrated under reduced pressure to yield a light yellow oil. The material was re-purified on a Teledyne ISCO Combiflash® Rf system using 1:1 DCM-EtOAc/MeOH (100:0→95:5) as eluent. The fractions containing product were combined and concentrated under reduced pressure to yield a light yellow solid (189.6 mg, 42%). 1H NMR (CDCl3, 400 MHz): δ=7.81-7.87 (m, 2H), 7.71 (s, 1H), 7.11 (s, 1H), 6.92 (d, J=7.8 Hz, 1H), 5.73-5.86 (m, 1H), 5.19-5.32 (m, 2H), 4.27 (t, J=6.4 Hz, 2H), 3.90-4.04 (m, 5H), 3.20 (d, J=16.2 Hz, 2H), 2.61 (dd, J=7.6, 17.4 Hz, 2H), 2.15-2.25 (m, 2H), 1.33 (s, 12H). MS (ESI): m/z 506.63 [M+H]+. UPLC: tR=1.23 min (UPLC-SQD: analytical—2 min).

1. customThe reaction mixture was quenched with water (10 mL)
2. extractionextracted with DCM (20 mL)
3. washThe organic layer was washed with NaHCO3 (10 mL)
4. washwashed with brine (15 mL)
5. dry with materialdried over anhydrous Na2SO4
6. filtrationfiltered
7. concentrationconcentrated under reduced pressure to a yellow oil
8. customThe crude material was purified on a Teledyne ISCO Combiflash® Rf system
9. additionThe fractions containing product
10. concentrationconcentrated under reduced pressure
11. customto yield a light yellow oil
12. customThe material was re-purified on a Teledyne ISCO Combiflash® Rf system
13. additionThe fractions containing product
14. concentrationconcentrated under reduced pressure