反应详情

To an oven-dried 3-necked 10 mL round-bottom flask under nitrogen was added 1-cyclopentyl-3-(2-(4-hydroxyphenyl)-1,1-bis(3-(trifluoromethoxy)phenyl)ethyl)urea, prepared as described in Procedure 11, 6, 2 and 59, (50 mg, 0.1 mmol), triphenylphosphine (34 mg, 0.1 mmol), ethyl 6-hydroxyhexanoate (17 mg, 0.1 mmol) and dry THF (0.5 mL). The reaction mixture was cooled in an ice-methanol bath and diethylazodicarboxylate (23 mg, 0.13 mmol) was added via syringe. The reaction was allowed to warm to rt and stirred overnight. The reaction mixture was concentrated in vacuo and purified by ISCO silica gel chromatography using a gradient of 5-25% EtOAc/hexanes as eluent to yield ethyl 6-(4-(2-(3-cyclopentylureido)-2,2-bis(3-(trifluoromethoxy)phenyl)ethyl)phenoxy)hexanoate (Example 313) was isolated as a white solid (43 mg, 61% yield). HPLC: RT=4.69 minutes (Phenomenex Luna C18 5μ column 4.6×50 mm eluting with 10-90% aqueous methanol containing 0.1% phosphoric acid over a 4 minute gradient monitoring at 220 nm). LC/MS [M+H] 711.3 (Phenomenex Luna C18 5μ column 4.6×30 mm eluting with 10-90% aqueous methanol containing 0.1% TFA over a 4 minute gradient monitoring at 220 nm). 1H NMR (400 MHz, CDCl3) δ ppm 7.33 (t, J=7.9 Hz, 2H), 7.20 (d, J=7.9 Hz, 2H), 7.12 (d, J=7.9 Hz, 2H), 7.07 (s, 2H), 6.62 (d, J=8.8 Hz, 2H), 6.56 (d, J=8.8 Hz, 2H), 4.10 (q, J=7.1 Hz, 2H), 3.86t, J=6.1 Hz, 2H), 3.68 (s, 1H), 3.62 (t, J=6.6 Hz, 1H), 2.30-2.27 (m, 2H), 1.82-1.14 (m, 17H), 1.23 (t, J=7.1 Hz, 3H).

1. customprepared
2. temperatureThe reaction mixture was cooled in an ice-methanol bath
3. concentrationThe reaction mixture was concentrated in vacuo
4. custompurified by ISCO silica gel chromatography