1,4-Dioxane hydrochloride → (R)-1-(4-chlorobenzyl)-3-(glycylamino)pyrrolidine

A 4 M HCl dioxane (38 mL) solution was added to a methanol (60 mL) solution of (R)-3-[N-(tert-butoxycarbonyl)glycyl]amino-1-(4-chlorobenzyl)pyrrolidine (5.39 g, 14.7 mmol). The resulting solution was stirred at room temperature for 2 hours. The reaction mixture was concentrated, and a 2 M solution (80 mL) of NaOH was added. The mixture solution was extracted with dichloromethane (80 mL×3), and the extracts were combined, dried over anhydrous sodium sulfate, concentrated and purified by column chromatography (SiO2, ethyl acetate/ethanol/triethylamine=90:5:5) to afford (R)-3-(glycylamino)-1-(4-chlorobenzyl)pyrrolidine (3.374 g, 86%) 1H NMR (CDCl3, 270 MHz) δ 1.77 (dd, J=1.3 and 6.9 Hz, 1H), 2.20-3.39 (m, 2H), 2.53 (dd, J=3.3 and 9.6 Hz, 1H), 2.62 (dd, J=6.6 and 9.6 Hz, 1H), 2.78-2.87 (m, 1H), 3.31 (s, 2H), 3.57 (s, 2H), 4.38-4.53 (br, 1H), 7.18-7.32 (m, 4H), 7.39 (br, s, 1H).

1. concentrationThe reaction mixture was concentrated
2. additiona 2 M solution (80 mL) of NaOH was added
3. extractionThe mixture solution was extracted with dichloromethane (80 mL×3)
4. dry with materialdried over anhydrous sodium sulfate
5. concentrationconcentrated
6. custompurified by column chromatography (SiO2, ethyl acetate/ethanol/triethylamine=90:5:5)

ORD record

ord-4ed2ce44c9e7423a8918491e0ab7b4f7

Source dataset

uspto-grants-2008_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07390830B1