N-Boc-2-amino-2-methyl-1-propanol 97

Uses

tert-Butyl (1-Hydroxy-2-methylpropan-2-yl)carbamate is used in preparation of diamine derivatives as KCa3.1 potassium channel inhibitors.

Synthesis

General procedure for the synthesis of 2-(Boc-amino)-2-methyl-1-propanol from di-tert-butyl dicarbonate and 2-amino-2-methyl-1-propanol: 230.4 mL of di-tert-butyl dicarbonate (1.00 mol) was added slowly and dropwise to a solution of di-tert-butyl dicarbonate (1.00 mol) at room temperature containing 98.05 g of 2-amino-2-methyl-1-propanol (1.10 mol) and 154 mL of triethylamine ( 1.10 mol) in a solution of dichloromethane (500 mL), and the titration process was continued for 20 minutes. The reaction mixture was continued to be stirred at room temperature for 2.5 hours. Upon completion of the reaction, the reaction mixture was concentrated under reduced pressure and the residue was diluted with 10% aqueous citric acid solution and subsequently extracted with ethyl acetate. The organic layers were combined, washed sequentially with water and saturated brine and dried over anhydrous magnesium sulfate. The desiccant was removed by filtration and the solvent was evaporated under reduced pressure to give 189.25 g of the crude product 2-(Boc-amino)-2-methyl-1-propanol in quantitative yield. The product was a colorless solid.1H NMR (CDCl3, 400 MHz) δ: 4.64 (br s, 1H), 4.01 (br s, 1H), 3.59 (d, 2H, J = 6.3 Hz), 1.43 (s, 9H), 1.25 (s, 6H).

References

[1] Journal of Organic Chemistry, 2000, vol. 65, # 20, p. 6368 - 6380
[2] Patent: EP2036896, 2009, A1. Location in patent: Page/Page column 149
[3] Journal of Organic Chemistry, 2005, vol. 70, # 4, p. 1188 - 1197
[4] Journal of Chemical Research, 2013, vol. 37, # 12, p. 757 - 760
[5] Patent: US6140326, 2000, A