Diisopropylethylamine → 4-(2-Benzyloxycarbonylamino-3-methyl-butyryl)-3-phenoxy-hexahydro-pyrrolo[3,2-b]pyrrole-1-carboxylic acid tert-butyl ester

온도

0 °C

To a solution containing Cbz-Val-OH (233 mg, 0.92 mmol) and crude 13 (256 mg, 0.84 mmol) in anhydrous NMP (3 mL) was cooled to 0° C. HATU (352 mg, 0.93 mmol) and DIPEA (125 mg, 1.01 mmol) were added and the reaction mixture was slowly warmed to ambient temperature. After 16 h, the reaction mixture was diluted with diethyl ether and EtOAc (1:4) and washed successively with 1M HCl, aqueous NaHCO3, water, and brine, dried over anhydrous Na2SO4, filtered, and concentrated. The crude product was purified by flash silica gel chromatography (4:1 hexanes/EtOAc) to afford 410 mg (90%) of 14 as a white solid. 1H NMR (CDCl3, 300 MHz), mixture of rotomers: δ7.31 (m, 9H), 6.96 (m, 1H), 5.79 (m, 1H). 5.07 (m, 2H), 4.91 (d, J=2.7 Hz, 1H), 4.51-4.43 (m, 2H), 4.35 (t, J=7.5 Hz, 1H), 4.07-3.99 (m, 2H), 3.90 (app d, J=26.4 Hz, 0.5H), 3.77 (app d, J=27.3 Hz, 0.5H), 3.31 (m, 2H), 2.49 (m, 0.5H), 2.35 (m, 0.5H), 1.92 (m, 1H), 1.51 (m, 9H), 0.95 (m, 6H) ppm.

1. temperaturethe reaction mixture was slowly warmed to ambient temperature
2. washwashed successively with 1M HCl, aqueous NaHCO3, water, and brine
3. dry with materialdried over anhydrous Na2SO4
4. filtrationfiltered
5. concentrationconcentrated
6. customThe crude product was purified by flash silica gel chromatography (4:1 hexanes/EtOAc)

ORD 기록

ord-567e39736ad2456ba7a415d72fa5e3d7

출처 데이터셋

uspto-grants-2013_04

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08415486B2