Chloroacetic Acid → (3S,4R)-tert-butyl 3-(4-bromo-2-nitrophenylamino)-4-(2-chloroacetoxy)pyrrolidine-1-carboxylate

To a mixture of (3S,4S)-tert-butyl 3-(4-bromo-2-nitrophenylamino)-4-hydroxypyrrolidine-1-carboxylate (2.50 mmol, 1.0 g), chloroacetic acid (3.0 mmol, 300 mg) and triphenylphosphine (3.0 mmol, 850 mg) in tetrahydrofuran (40 mL) add diethylazodicarboxylate (3.0 mmol, 600 mg) and stir at room temperature for 12 h. Remove the solvent, add ethyl acetate (50 mL) to the residue and wash with water and brine. Dry over anhydrous sodium sulfate and evaporate. Purify the residue by column chromatography, eluting with 20% ethyl acetate in methylene chloride to obtain the title compound as a yellow solid (1.10 g, 98%). 1H NMR (500 MHz, CDCl3) δ 8.35 (s, 1H), 8.20 (m, 1H), 7.60 (m, 1H), 6.82 (m, 1H), 5.55 (d, J=6.8 Hz, 1H), 4.32 (m, 1H), 4.13 (bd, J=8.2 Hz, 2H), 3.90 (m, 1H), 3.79 (m, 1H), 3.74 (dd, J=4.2, 10.4 Hz, 1H), 3.25 (t, J=7.20 Hz, 1H), 1.41 (s, 9H).

1. customRemove the solvent
2. additionadd ethyl acetate (50 mL) to the residue
3. washwash with water and brine
4. dry with materialDry over anhydrous sodium sulfate
5. customevaporate
6. customPurify the residue by column chromatography
7. washeluting with 20% ethyl acetate in methylene chloride

ORD-Eintrag

ord-ed463b4db4854657ad6f62a7d5cafb0f

Quelldatensatz

uspto-grants-2011_08

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07994164B2