Lithium diisopropylamide → (S)-1-(2-Azido-benzoyl)-5-oxo-pyrrolidine-2-carboxylic acid tert-butyl ester

A stirred solution of (2S)-5-oxo-proline tert-butyl ester (T. Kolasa and M. J. Miller, J. Org. Chem., 1990, 55, 1711-1721) (1.13 g, 6.13 mmol) in anhydrous THF (15 mL) was treated at −78° C. with LDA (9.19 mmol) and the reaction was stirred for 15 min. A solution of 2-azidobenzoyl chloride (T. Okawa, T. Sugimori, S. Eguchi and A. Kakehi, Heterocycles, 1998, 47, 1, 375-382) (6.13 mmol) in anhydrous THF (5 mL) was then added dropwise and the reaction mixture was stirred at −78° C. for 1 h before being quenched with saturated aq.NH4Cl. The reaction was allowed to warm to room temperature and the organic layer was washed with saturated aq.NH4Cl, dried (MgSO4), filtered and evaporated to give an oil which was purified by flash chromatography (20% ethyl acetate in hexane) to afford the title compound as a pale yellow oil (1.67 g, 82%): 1H NMR (400 MHz, CDCl3) δ 1.53 (9H, s), 2.14 (1H, m), 2.43 (1H, m), 2.55 (1H, m), 2.69 (1H, m), 4.79 (1H, dd, J 9.2, 3.2 Hz), 7.19-7.22 (2H, m), 7.36 (1H, m), 7.49 (1H, m). 13C NMR (100 MHz, CDCl3) δ 22.1 (CH2), 28.3 (CH3), 31.9 (CH2), 59.3 (CH), 83.0 (C), 118.7 (CH), 125.0 (CH), 127.9 (C), 129.1 (CH), 131.9 (CH), 137.9 (C), 167.5 (C), 170.2 (C), 173.6 (C).

1. stirringthe reaction mixture was stirred at −78° C. for 1 h
2. custombefore being quenched with saturated aq
3. washthe organic layer was washed with saturated aq
4. dry with materialNH4Cl, dried (MgSO4)
5. filtrationfiltered
6. customevaporated
7. customto give an oil which
8. customwas purified by flash chromatography (20% ethyl acetate in hexane)

ORD record

ord-82182b2aebe64aa49e825417eeb2cc1a

Source dataset

uspto-grants-2010_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07829561B2