Carbamic acid, (6-methyl-3-pyridinyl)-, 1,1-dimethylethyl ester (9CI) Chemical Properties

Melting point:

114-115 °C(Solv: hexane (110-54-3); ethyl acetate (141-78-6))

Boiling point:

262.7±28.0 °C(Predicted)

Density 

1.108±0.06 g/cm3(Predicted)

storage temp. 

Sealed in dry,Room Temperature

pka

12.94±0.70(Predicted)

Appearance

White to off-white Solid

Carbamic acid, (6-methyl-3-pyridinyl)-, 1,1-dimethylethyl ester (9CI) Usage And Synthesis

Synthesis

Step 1. Synthesis of tert-butyl (6-methylpyridin-3-yl)carbamate. Di-tert-butyl dicarbonate (55.5 g, 298 mmol) was slowly added dropwise to a solution of 6-methylpyridin-3-amine (25 g, 231 mmol) in ethanol (100 mL) at 0 °C. After the dropwise addition, the reaction mixture was stirred at room temperature overnight. The progress of the reaction was monitored by TLC (unfolding agent: petroleum ether/ethyl acetate, 2:1) to confirm complete consumption of 6-methylpyridin-3-amine. Upon completion of the reaction, the reaction mixture was filtered and the filter cake was washed with ethanol (30 mL x 3). The filtrates were combined and concentrated under reduced pressure to give a yellow residue. This residue was purified by column chromatography (eluent: petroleum ether/ethyl acetate, 4:1 to 1:1) to afford tert-butyl (6-methylpyridin-3-yl)carbamate (32.5 g, 67.4% yield) as a white solid.1H NMR (400 MHz, CDCl3) δ 8.30 (d, J = 2.0 Hz, 1H), 7.86 (br s, 1H) 7.10 (d, J = 8.5 Hz, 1H), 6.57 (br s, 1H), 2.49 (s, 3H), 1.51 (s, 9H). Step 2. Synthesis of racemic-cis/trans-tert-butyl (6-methylpiperidin-3-yl)carbamate. Platinum oxide (2.5 g) was added to a dry hydrogenation flask under argon protection. Then a solution of tert-butyl (6-methylpyridin-3-yl)carbamate (33 g, 158.5 mmol) in acetic acid (300 mL) was added, and the resulting mixture was hydrogenated at 50 °C under 55 psi hydrogen pressure for 30 hours. The progress of the reaction was monitored by TLC (unfolding agent: petroleum ether/ethyl acetate, 2:1) to confirm complete consumption of the starting material. Upon completion of the reaction, the reaction mixture was filtered and the filter cake was washed with methanol (50 mL x 2). The filtrates were combined and evaporated under reduced pressure to afford tert-butyl (6-methylpiperidin-3-yl)carbamate (34 g, 100% yield) as a yellow oil (cis/trans ratio 2:1), which was used directly in the next step of the reaction without further purification.LC/MS (M + H) 215.2.

References

[1] Patent: US2015/158864, 2015, A1. Location in patent: Paragraph 0270
[2] Journal of Medicinal Chemistry, 2017, vol. 60, # 5, p. 1971 - 1993
[3] Patent: WO2012/148775, 2012, A1. Location in patent: Page/Page column 113; 114
[4] Patent: WO2010/16005, 2010, A1. Location in patent: Page/Page column 135-136
[5] Bioorganic and Medicinal Chemistry Letters, 2016, vol. 26, # 22, p. 5580 - 5590

Carbamic acid, (6-methyl-3-pyridinyl)-, 1,1-dimethylethyl ester (9CI)(323578-37-6)Related Product Information

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