1-Amino-2-methylpropan-2-ol

Chemical Properties

Pale yellow liquid

Uses

3-Amino-2-methyl-2-propanol, is a versatile intermediate used for the synthesis of more complex compounds, including inhibitors. It is an intermediate in the preparation of metabolites of Darunavir (D193500), such as (A581405).

Synthesis

The general procedure for the synthesis of 1-amino-2-methyl-2-propanol from acetone cyanohydrin is as follows: Step A: Synthesis of 1-amino-2-methyl-2-propanol [Chem.17] To a tetrahydrofuran (180 mL) suspension of lithium aluminum hydride (6.08 g, 160 mmol), a tetrahydrofuran (20 mL) solution of acetone cyanohydrin (7.32 mL, 80.0 mmol) was slowly added dropwise over a controlled period of 15 min at 0 °C. The reaction mixture was then refluxed for 4 hours. Upon completion of the reaction, the mixture was cooled to 0 °C and the reaction was quenched with sodium sulfate decahydrate and potassium fluoride. After continued stirring at 35°C for 30 minutes, the mixture was filtered through a diatomaceous earth pad. The filtrate was concentrated in vacuum to give the oily product 1-amino-2-methyl-2-propanol (3.98 g, 56% yield). [0229] 1H-NMR (300 MHz, CDCl3) δ: 2.60 (s, 2H), 1.69 (s, 6H), no peaks for OH and NH2 were observed.

References

[1] Journal of Medicinal Chemistry, 2012, vol. 55, # 9, p. 4336 - 4351
[2] Patent: WO2010/84767, 2010, A1. Location in patent: Page/Page column 50-51
[3] Tetrahedron Letters, 1996, vol. 37, # 40, p. 7319 - 7322
[4] Journal of Medicinal Chemistry, 1998, vol. 41, # 18, p. 3347 - 3359
[5] Patent: EP1591446, 2005, A1. Location in patent: Page/Page column 96