Ethyl phenylacetate → 3-Cyclopentyl-2-phenylpropionic acid methyl ester

Temperatur

-78 °C

To a 500 mL round bottom flask containing 250 mL of 9:1 THF/DMPU at −78° C. is added 17 mL DIEA followed by rapid addition of 49 mL of 2.5 M n-BuLi/hexanes. After 10 min at −78° C., a solution of ethyl phenylacetate (17.0 g, 113 mmol) in 50 mL of 9:1 THF/DMPU is added dropwise over 15-20 min. A yellow solution results, and the reaction mixture is stirred at −78° C. for 30-45 min. A solution of 26.7 g (115 mmol) of freshly prepared cyclopentyl triflate (title B compound in Example 1) in 25 mL 9:1 THF/DMPU is added dropwise over 10-15 min. The mixture is then stirred over 2-3 h to ambient temperature. The reaction is quenched into 300 mL of 1 N HCl and extracted 3 times with methyl-t-butylether (MTBE). The combined extracts are washed with saturated NaCl and dried over anhydrous magnesium sulfate. Filtration and evaporation afford crude product as a yellow oil. Flash chromatography over silica gel eluting with 4:1 hexane/MTBE affords 3-cyclopentyl-2-phenylpropionic acid methyl ester as a light yellow oil: 1H NMR (400 MHz, CDCl3) δ 1.1 (m, 2H), 1.3 (m, 1H), 1.50 (m, 2H), 1.6 (m, 2H), 1.7 (m, 2H), 2.1(dt, J=13.4, 7.7 Hz, 1H), 3.60 (m, 1H), 3.64 (s, 3H), 7.3 (m, 5H); LC/MS 233 (M+1).

1. customA yellow solution results
2. stirringThe mixture is then stirred over 2-3 h to ambient temperature
3. customThe reaction is quenched into 300 mL of 1 N HCl
4. extractionextracted 3 times with methyl-t-butylether (MTBE)
5. washThe combined extracts are washed with saturated NaCl
6. dry with materialdried over anhydrous magnesium sulfate
7. filtrationFiltration and evaporation
8. customafford crude product as a yellow oil

ORD-Eintrag

ord-c5502773db374f7da37eba39904963e3

Quelldatensatz

uspto-grants-2012_08

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08252931B2