Hydrochloric Acid → 3-(4-Carboxymethyl-phenyl)-2,2-dimethyl-propionic acid ethyl ester

温度

-78 °C

To a solution of diisopropylamine (13.11 mmol, 1.8 mL) in anhydrous tetrahydrofuran (40 mL) cooled to −78° C. under a nitrogen atmosphere was added 2.5M n-BuLi in hexanes (13.11 mmol, 5.24 mL). The resulting solution was allowed to stir at −78° C. for 20 minutes, warmed to room temperature for 10 minutes, then cooled back to −78° C. for 10 minutes. The mixture was added to a solution of ethyl isobutyrate (13.11 mmol, 1.76 mL) dissolved in anhydrous tetrahydrofuran (20 mL) cooled to −78° C. The resulting solution was allowed to stir at −78° C. for 1 h. (4-Bromomethyl-phenyl)-acetic acid (1 g, 4.37 mmol) in anhydrous tetrahydrofuran (10 mL) was added to the solution dropwise. The solution was warmed to room temperature and was allowed to stir for 20 minutes. The reaction mixture was poured over a dilute HCl solution (1 N). The aqueous layer was isolated and extracted with diethyl ether (1×). The organic layers were combined, washed with 2N HCl (2×), brine (1×), dried over anhydrous sodium sulfate, and concentrated to a crude oil. The oil was chromatographed on silica gel (Merck silica gel 60, art#9385-3) eluting with 10% methanol/methylene chloride to give 3-(4-carboxymethyl-phenyl)-2,2-dimethyl-propionic acid ethyl ester as a white solid (0.97 g, 84%).

1. temperaturewarmed to room temperature for 10 minutes
2. temperaturecooled back to −78° C. for 10 minutes
3. temperaturecooled to −78° C
4. additionwas added to the solution dropwise
5. temperatureThe solution was warmed to room temperature
6. stirringto stir for 20 minutes
7. customThe aqueous layer was isolated
8. extractionextracted with diethyl ether (1×)
9. washwashed with 2N HCl (2×), brine (1×)
10. dry with materialdried over anhydrous sodium sulfate
11. concentrationconcentrated to a crude oil
12. customThe oil was chromatographed on silica gel (Merck silica gel 60, art#9385-3)
13. washeluting with 10% methanol/methylene chloride

ORDレコード

ord-13af006dbb66434e9e63d0314102259a

出典データセット

uspto-grants-2004_03

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US06699904B2