3-(difluoromethoxy)pyridin-2-amine

3-(difluoromethoxy)pyridin-2-amine Property

Boiling point:

228.6±35.0 °C(Predicted)

Density 

1.331±0.06 g/cm3(Predicted)

storage temp. 

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

pka

7.36±0.10(Predicted)

Appearance

Off-white to brown Solid

Safety

HS Code 

2933399990

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H302Harmful if swallowed

H315Causes skin irritation

H319Causes serious eye irritation

H335May cause respiratory irritation

Precautionary statements

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

P301+P312IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

3-(difluoromethoxy)pyridin-2-amine Chemical Properties,Usage,Production

Synthesis

General procedure for the synthesis of 3-(difluoromethoxy)pyridin-2-amine from 3-(difluoromethoxy)-2-nitropyridine: 3-(difluoromethoxy)-2-nitropyridine (450 mg, 2.37 mmol) was dissolved in a mixed solvent of ethanol (2 mL) and acetic acid (2 mL) and reduced iron powder (397 mg, 7.10 mmol) was added. The reaction mixture was stirred at 100 °C overnight. Since the ingredients were not fully reacted, reduced iron powder (397 mg, 7.10 mmol) was added again and stirring was continued at 100 °C overnight. After completion of the reaction, the mixture was filtered through diatomaceous earth and the filtrate was concentrated under reduced pressure. To the concentrated residue was added saturated aqueous sodium bicarbonate and extracted three times with ethyl acetate. The organic layers were combined, dried with anhydrous magnesium sulfate, filtered and purified by silica gel column chromatography (eluent: chloroform/methanol=9/1, v/v) to afford the target product 3-(difluoromethoxy)pyridin-2-amine (250 mg, 66% yield). The product was detected by electrospray ionization mass spectrometry (ESIMS), m/z: 161 (M + H)+; 1H NMR (270 MHz, CDCl3, δ): 4.79 (broad single peak, 2H), 6.14-6.80 (multiple peaks, 2H), 7.19-7.35 (multiple peaks, 1H), 7.85-7.98 (multiple peaks, 1H).

References

[1] Patent: WO2010/100127, 2010, A1. Location in patent: Page/Page column 73
[2] Patent: WO2009/16460, 2009, A2. Location in patent: Page/Page column 55-56
[3] Patent: EP2740730, 2014, A1. Location in patent: Paragraph 0346
[4] Patent: WO2014/111496, 2014, A1. Location in patent: Page/Page column 108
[5] Patent: WO2015/91889, 2015, A1. Location in patent: Page/Page column 73; 74