反应详情

To a solution of (R)-4-(3′-chlorobiphenyl-4-yl)-3-(2-(prop-1-en-2-yl)oxazole-5-carboxamido)butanoic acid (60 mg, 0.14 mmol) in DCM (2 mL) and MeOH (2 mL) at −78° C. is bubbled ozone for 30 seconds. After 30 seconds ozone is removed and oxygen is bubbled for 10 minutes. After bubbling oxygen for 10 minutes the −78° C. bath is removed and the reaction is quenched with polymer supported triphenylphosphine and the reaction is stirred at room temperature for 2 hours. After 2 hours the reaction is filtered to remove triphenylphosphineoxide on supported polymer and the filtrate is collected and concentrated under reduced pressure. The obtained residue is purified by RP-HPLC (SunFire C18, H2O (0.1% TFA)/CH3CN), and then lyophilized to give (R)-3-(2-acetyloxazole-5-carboxamido)-4-(3′-chlorobiphenyl-4-yl)butanoic acid (13 mg). HPLC retention time=1.67 minutes (condition D); MS (m+1)=427.0; 1H NMR (400 MHz, DMSO-d6) δ ppm 2.53-2.59 (m, 2 H) 2.60 (s, 3 H) 2.87 (dd, J=10.9, 3.3 Hz, 1 H) 2.94 (dd, J=10.9, 5.1 Hz, 1 H) 4.46-4.60 (m, 1 H) 7.31 (d, J=8.1 Hz, 2 H) 7.36-7.43 (m, 1 H) 7.47 (t, J=7.8 Hz, 1 H) 7.62 (d, J=8.3 Hz, 3 H) 7.69 (t, J=1.9 Hz, 1 H) 7.94 (s, 1 H) 8.86 (d, J=8.6 Hz, 1 H) 12.31 (br. s., 1 H).

1. customAfter 30 seconds ozone is removed
2. customoxygen is bubbled for 10 minutes
3. customAfter bubbling oxygen for 10 minutes the −78° C. bath
4. customis removed
5. customthe reaction is quenched with polymer
6. filtrationAfter 2 hours the reaction is filtered
7. customto remove triphenylphosphineoxide
8. customthe filtrate is collected
9. concentrationconcentrated under reduced pressure
10. customThe obtained residue is purified by RP-HPLC (SunFire C18, H2O (0.1% TFA)/CH3CN)