Triethylamine → Methyl 6-(2-phenoxyacetylamino)hexanoate

To phenoxyacetic acid (50.0 g, 0.33 mol) dissolved in tetrahydrofuran (210 mL) was slowly added 1,1′-carbonyldiimidazole (56.0 g, 0.35 mol) with additional tetrahydrofuran (30 mL). After stirring for 1.5 hr at room temperature, triethylamine (92 mL, 0.66 mol) was added all at once and methyl 6-aminohexanoate hydrochloride (66.0 g, 0.36 mol) was added in portions over 20 min. The reaction mixture was stirred at room temperature overnight, heated at 50° C. for 20 min, and then stirred at room temperature for 20 hr. The reaction mixture was concentrated under reduced pressure, added to 1 N hydrochloric acid (750 mL) and extracted with ethyl acetate (2×250 mL). The combined organic layers were washed with 1 N hydrochloric acid (1×100 mL), water (1×100 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give a yellow oil. NMR analysis indicated presence of phenoxyacetic acid. The concentrate was dissolved in toluene (450 mL) and stirred 15 min with 25% sodium bicarbonate (200 mL). The organic layer was filtered through 1 PS paper, concentrated under reduced pressure, diluted with hexanes, and concentrated again, to give 76.89 g (84%) of the title compound, amide, as a yellow oil.

1. additionwas added in portions over 20 min
2. stirringThe reaction mixture was stirred at room temperature overnight
3. temperatureheated at 50° C. for 20 min
4. stirringstirred at room temperature for 20 hr
5. concentrationThe reaction mixture was concentrated under reduced pressure
6. additionadded to 1 N hydrochloric acid (750 mL)
7. extractionextracted with ethyl acetate (2×250 mL)
8. washThe combined organic layers were washed with 1 N hydrochloric acid (1×100 mL), water (1×100 mL)
9. dry with materialdried over anhydrous sodium sulfate
10. concentrationconcentrated under reduced pressure
11. customto give a yellow oil
12. filtrationThe organic layer was filtered through 1 PS paper
13. concentrationconcentrated under reduced pressure
14. additiondiluted with hexanes
15. concentrationconcentrated again

ORD-Eintrag

ord-59910d806a99497eb456c4d3c860b5ba

Quelldatensatz

uspto-grants-2007_11

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07294716B2