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

To a stirred solution of 3-(4-carboxymethyl-phenyl)-2,2-dimethyl-propionic acid ethyl ester (0.97 g, 3.67 mmol) in chloroform (15 mL) under an nitrogen atmosphere was added thionyl chloride (11 mmol, 0.804 mL). The mixture was heated under reflux for 2.75 hours, cooled to room temperature and concentrated under reduced pressure to a clear oil. The oil was dissolved in methylene chloride (0.50 mL) then added dropwise to a solution of 1-heptylamine (4.40 mmol, 0.653 mL) and N,N-diisopropylethylamine (4.40 mmol, 0.765 mL) in anhydrous dichloromethane (5 mL) cooled to 0° C. The solution was warmed to room temperature and allowed to stir for 30 minutes, then was poured over a solution of 1 M HCl (10 mL). The aqueous layer was isolated and extracted with diethyl ether (2×). The organic layers were combined, washed with 2N HCl (2×), brine (1×), dried over anhydrous sodium sulfate and concentrated under reduced pressure to give crude 3-(4-heptylcarbamoylmethyl-phenyl)-2,2-dimethyl-propionic acid ethyl ester as an orange oil. The oil was used in the preparation of 3-[4-(2-heptylamino-ethyl)-phenyl]-2,2-dimethyl-propionic acid ethyl ester without further purification. (1.27 g, 95%).

1. temperatureThe mixture was heated
2. temperatureunder reflux for 2.75 hours
3. concentrationconcentrated under reduced pressure to a clear oil
4. dissolutionThe oil was dissolved in methylene chloride (0.50 mL)
5. temperaturecooled to 0° C
6. temperatureThe solution was warmed to room temperature
7. customThe aqueous layer was isolated
8. extractionextracted with diethyl ether (2×)
9. washwashed with 2N HCl (2×), brine (1×)
10. dry with materialdried over anhydrous sodium sulfate
11. concentrationconcentrated under reduced pressure

ORD record

ord-4bd769b2ef1a44039cece36e82343f71

Source dataset

uspto-grants-2004_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06699904B2