Ethyl 3-phenylprop-2-enoate → Ethyl (2E)-3-(4-{[(1-aminocyclopentyl)carbonyl]amino}phenyl)acrylate

온도

40 °C

1-{[(benzyloxy)carbonyl]amino}cyclopentanecarboxylic acid was dissolved in DMF (0.2 M). HATU (1 eq.) and triethylamine (3 eq.) were added, followed by ethyl cinnamate (0.95 eq.). The resulting mixture was stirred for 48 h at 40° C. DMF was evaporated, the resulting oil taken up in EtOAc and the solution washed with HCl (3×, 1 M), water, a solution of saturated aqueous NaHCO3 (2×) and brine. Drying over Na2SO4 and evaporation gave an orange solid, which was purified by flash chromatography on silica gel using PE/EtOAc (2.5:1, containing 1% EtOH) as the eluent. The resulting solid was immediately dissolved in DCM (0.1M) and triflic acid (5 eq.) was added dropwise at RT. After 5 min at RT, the red mixture was poured into an aqueous solution of NaHCO3. The organic phase was separated, the aqueous phase was extracted with DCM (4×) and the combined organic phases dried over Na2SO4. Evaporation gave the title compound as an off-white solid, which was used without further purification. 1H NMR (400 MHz, DMSO-d6, 300 K) δ 1.26 (t, J 7.1, 3H), 1.48-1.61 (m, 2H), 1.63-1.87 (m, 4H), 1.96-2.10 (m, 2H), 4.18 (q, J 7.1, 2H), 6.53 (d, J 16.0, 1H), 6.60-7.30 (bs, 3H), 7.59 (d, J 16.0, 1H), 7.67 (d, J 8.5, 2H), 7.76 (d, J 8.5, 2H); MS (ES+) m/z 303 (M+H)+.

1. customDMF was evaporated
2. washthe solution washed with HCl (3×, 1 M), water
3. dry with materialDrying over Na2SO4 and evaporation
4. customgave an orange solid, which
5. customwas purified by flash chromatography on silica gel using PE/EtOAc (2.5:1, containing 1% EtOH) as the eluent
6. dissolutionThe resulting solid was immediately dissolved in DCM (0.1M)
7. waitAfter 5 min at RT
8. customThe organic phase was separated
9. extractionthe aqueous phase was extracted with DCM (4×)
10. dry with materialthe combined organic phases dried over Na2SO4
11. customEvaporation

ORD 기록

ord-cc06da5ddd26472080f6b3d7b7d9a37c

출처 데이터셋

uspto-grants-2010_09

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US07795250B2