N,N'-Dimethylethylenediamine → HCID 72305307, compound

To a small reaction tube fitted with a screw cap is placed (4S,5S)-4-(3-methoxyphenyl)-5-(prop-2-ynyl)oxazolidin-2-one (50 mg, 0.22 mmol) in tBuOH/water (1:1, 1.5 mL). Successively, copper(II) sulfate pentahydrate (2 mg, 0.012 mmol), sodium ascorbate (12 mg, 0.06 mmol), potassium bicarbonate (92 mg, 0.92 mmol), and the freshly prepared product described above are then added. After stirring at room temperature for 2 h, the reaction is then quenched with sat. ammonium chloride, and extracted with EtOAc. The combined organics are washed with brine, dried over MgSO4, filtered, and concentrated to give the crude product, which is carried forward without purification. Next, in a small reaction tube fitted with a screw cap is placed the crude intermediate, acetonitrile (1 mL), 4-chloro-1-iodobenzene (62 mg, 0.26 mmol), copper iodide (3 mg, 0.04 mmol), N,N′-dimethylethylenediamine (9.3 μL, 0.08 mmol), and cesium carbonate (143 mg, 0.44 mmol). The vessel is evacuated and back-filled with nitrogen, then heated to 85° C. for 4 h. The reaction is then cooled to room temperature and quenched with sat. ammonium chloride, extracted with EtOAc, dried over MgSO4, filtered, and concentrated. The title compound is obtained after purification by preparative HPLC (C-18, 10-90% ACN/water (0.05% TFA)). 1H NMR (acetone-d6, 400 MHz) 5 (mixture of diastereomers) 8.67 (overlp s, 1H), 7.50-7.43 (m, 2H), 7.30-7.27 (m, 2H), 6.97-6.96 (m, 2H), 6.90-6.87 (m, 1H), 5.45 (d, J=4.8 Hz, 0.2H), 5.40 (d, J=5.8 Hz, 0.8H), 4.92-4.89 (m, 0.2H), 4.68-4.63 (m, 0.8H), 4.05 (m, 1H), 3.97-3.68 (m, 7H), 2.34-2.01 (m, 2H); HPLC-MS calculated C23H23ClN2O5 (M+H+) 455.1, found 455.1. For references to Copper catalyzed synthesis of 3,5-disubstituted isoxazoles, see Hansen, T. V.; Wu, P.; Fokin, V. V. J. Org. Chem. 2005, 70, 7791-7764; Himo, F.; Lovell, T.; Hilgraf, R.; Rostovtsev, V. V.; Noodleman, L.; Sharpless, K. B.; Fokin, V. V. J. Am. Chem. Soc. 2005, 127, 210-216.

1. customTo a small reaction tube fitted with a screw
2. customcap
3. customthe reaction is then quenched with sat. ammonium chloride
4. extractionextracted with EtOAc
5. washThe combined organics are washed with brine
6. dry with materialdried over MgSO4
7. filtrationfiltered
8. concentrationconcentrated
9. customto give the crude product, which
10. customis carried forward without purification
11. customNext, in a small reaction tube fitted with a screw
12. customcap
13. customThe vessel is evacuated
14. additionback-filled with nitrogen
15. temperatureheated to 85° C. for 4 h
16. temperatureThe reaction is then cooled to room temperature
17. customquenched with sat. ammonium chloride
18. extractionextracted with EtOAc
19. dry with materialdried over MgSO4
20. filtrationfiltered
21. concentrationconcentrated

ORD record

ord-37a3f3138b1146d8979c502ae604940a

Source dataset

uspto-grants-2013_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08431607B2