TERT-BUTYL 4-CHLORO-3-IODOPYRIDIN-2-YLCARBAMATE Chemical Properties

Boiling point:

334.1±42.0 °C(Predicted)

Density 

1.723±0.06 g/cm3(Predicted)

storage temp. 

under inert gas (nitrogen or Argon) at 2–8 °C

pka

11.10±0.70(Predicted)

Appearance

off-white solid

TERT-BUTYL 4-CHLORO-3-IODOPYRIDIN-2-YLCARBAMATE Usage And Synthesis

Synthesis

General procedure for the synthesis of tert-butyl 4-chloro-3-iodopyridin-2-yl carbamate from 2-BOC-amino-4-chloropyridine: tert-butyl (4-chloropyridin-2-yl)carbamate (5 g, 21.87 mmol) was added to a 250 mL round bottom flask and dissolved in tetrahydrofuran (THF, 109 mL). The stirred solution was cooled to -78 °C in a dry ice bath. Subsequently, N,N,N',N'-tetramethylethylenediamine (TMEDA, 8.25 mL, 54.7 mmol) was added and the flask was flushed with nitrogen. Next, a hexane solution (21.87 mL, 54.7 mmol) of 2.5 M n-butyllithium (n-BuLi) was slowly added over 30 min. The mixture was stirred at -78 °C for 1 h and then treated dropwise with a solution of anhydrous THF (16 mL) with iodine (13.87 g, 54.7 mmol) at -78 °C. After dropwise addition, the reaction was continued to stir at -78 °C for 30 min and then slowly warmed to room temperature. The reaction mixture was treated with a solution of sodium bisulfite (16 g) in water (100 mL), stirred for 30 min and subsequently extracted with ethyl acetate (EtOAc). The organic phase was washed with brine, dried over anhydrous magnesium sulfate (MgSO4) and concentrated under reduced pressure. The product was purified by fast chromatography: using a 90 g silica gel column equilibrated first with dichloromethane (DCM), after loading the sample, 0 mL of the initial waste solution was collected, and the grades were sized at 27 mL (18 × 150 mm column) and eluted with a gradient of methanol (MeOH) in dichloromethane (0% [180 mL], 0-5% [360 mL], 5% [700 mL]). The grades containing the product were collected and concentrated under reduced pressure to give tert-butyl (4-chloro-3-iodopyridin-2-yl)carbamate (6.59 g, 85% yield) as a yellow solid.1H NMR (400 MHz, chloroform-d) δ ppm 8.28 (d, J = 5.0 Hz, 1H), 7.43 (br.s, 1H), 7.10 (d, J = 5.0 Hz. 1H), 1.56 (s, 9H).

References

[1] Patent: US2013/245042, 2013, A1. Location in patent: Paragraph 0040
[2] Patent: US2005/245530, 2005, A1. Location in patent: Page/Page column 46
[3] Journal of Medicinal Chemistry, 2009, vol. 52, # 5, p. 1251 - 1254
[4] Bioorganic and Medicinal Chemistry Letters, 2016, vol. 26, # 1, p. 114 - 120
[5] Molecules, 2012, vol. 17, # 9, p. 10683 - 10707,25

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