Tetrahydrofuran → 4-(Tert-butoxycarbonylamino)-2-(4-chlorobenzyl)butanoic acid

LHMDS (28.3 mL, 28.3 mmol) was diluted into THF (90 mL) and cooled to −78° C. tert-Butyl 2-oxopyrrolidine-1-carboxylate (5.00 g, 27.0 mmol) was dissolved into THF (35 mL) and added to the LHMDS over a 5 minute period at −78° C. The reaction was allowed to stir for 45 minutes, and then a THF (35 mL) solution of 1-(bromomethyl)-4-chlorobenzene (5.82 g, 28.3 mmol, 1.05 equiv) was added. The reaction was allowed to stir at −78° C. for 1 hour, and then warmed to room temperature over 3 hours. The mixture was quenched with the addition of a 3M LiOH solution (90 mL) and stirred for 48 hours at room temperature. The reaction was then diluted with water and washed with ethyl acetate. The aqueous layer was acidified with 3M HCl and extracted several times with ethyl acetate. The combined organic fractions were washed with water, dried over MgSO4, filtered, and concentrated to give the crude product. The crude product was purified by column chromatography (60:40 hexanes:ethyl acetate) to give 4-(tert-butoxycarbonylamino)-2-(4-chlorobenzyl)butanoic acid (0.84 g, 9.4%).

1. stirringto stir at −78° C. for 1 hour
2. customThe mixture was quenched with the addition of a 3M LiOH solution (90 mL)
3. stirringstirred for 48 hours at room temperature
4. additionThe reaction was then diluted with water
5. washwashed with ethyl acetate
6. extractionextracted several times with ethyl acetate
7. washThe combined organic fractions were washed with water
8. dry with materialdried over MgSO4
9. filtrationfiltered
10. concentrationconcentrated
11. customto give the crude product
12. customThe crude product was purified by column chromatography (60:40 hexanes:ethyl acetate)

ORD-Eintrag

ord-3343d5e3f3764eea883a55b15489d232

Quelldatensatz

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08841304B2