tert-Butyl (4-chloro-3-formylpyridin-2-yl)carbamate

tert-Butyl (4-chloro-3-formylpyridin-2-yl)carbamate Property

storage temp. 

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

form 

solid

Appearance

Off-white to light yellow Solid

Safety

Risk Statements 

43

Safety Statements 

36/37

HazardClass 

IRRITANT

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H302Harmful if swallowed

H317May cause an allergic skin reaction

Precautionary statements

P280Wear protective gloves/protective clothing/eye protection/face protection.

tert-Butyl (4-chloro-3-formylpyridin-2-yl)carbamate Chemical Properties,Usage,Production

Synthesis

The general procedure for the synthesis of tert-butyl 4-chloro-3-formylpyridine-2-carbamate from 2-BOC-amino-4-chloropyridine and N,N-dimethylformamide was as follows: firstly, tert-butyl (4-chloropyridin-2-yl)carbamate (15.0 g, 65.59 mmol) was dissolved in THF (300 mL) and the solution was cooled down to -78 °C. Under stirring, nBuLi (55.1 mL, 2.50 M, 137.7 mmol) was slowly added dropwise over 20 min. The reaction mixture was continued stirring at -78 °C for 30 min to form a pale yellow solution. Subsequently, DMF (15.1 mL, 196.8 mmol) was added dropwise over 5 minutes and stirring was continued at -78 °C for 1 hour. Upon completion of the reaction, the reaction was quenched with MeOH (2 eq.) and subsequently concentrated. After addition of HCl (16 mL), the mixture was concentrated again. The residue was suspended in EtOAc and washed sequentially with 5% NaHCO3 solution and brine before evaporating the solvent. The crude product was suspended in hexane (100 mL) and the precipitate was collected by filtration to afford the target intermediate tert-butyl 4-chloro-3-formylpyridine-2-carbamate (12.8 g, 76% yield) as a white solid.

References

[1] Patent: US2012/190654, 2012, A1. Location in patent: Page/Page column 12
[2] Journal of Medicinal Chemistry, 2010, vol. 53, # 8, p. 3330 - 3348
[3] Patent: WO2018/170284, 2018, A1. Location in patent: Paragraph 00263
[4] Journal of Medicinal Chemistry, 2009, vol. 52, # 5, p. 1251 - 1254
[5] Patent: US2013/237555, 2013, A1. Location in patent: Paragraph 0168