(R)-3-amino-1-butanol

Description

(R)-3-amino-1-butanol is an alcohol organic compound, which is a key intermediate for many chiral drugs.

The Uses of (R)-3-amino-1-butanol

(R)-3-Aminobutan-1-ol, can be used as an intermediate in the preparation of compounds having HIV integrase inhibitory activity.

Definition

(R)-3-amino-1-butanol is the most critical building block for synthesizing pharmaceuticals, including Dolutegravir, penicillium antibiotics, and anti-tumor drug 4-methylcyclophosphamide. Mainly, Dolutegravir is a new-generation integrase inhibitor for the treatment of HIV infection[1]. Currently, this compound is mainly achieved by chemical methods. A ruthenium complex could be used to catalyze the hydrogen reduction of (R)-3-aminobutyric acid ester to (R)-3-amino-1-butanol[2].

Synthesis

The (S)-mandelic salt of (R)-3-amino-1-butanol (372 g, 1.54 mol) was suspended in triethanolamine (1 I) at 80° C., and the slurry was admixed with sodium methoxide (277.6 g, 1.54 mol; 30% in methanol), which gave a clear solution. This was heated to 100° C. and vacuum was applied. In a stepwise manner, a pressure of 750, 500, 250, 100, 50 and finally 20 mbar was applied. Through an attached Claisen distillation head (no return stream, no column), a clear distillate distilled over at a top temperature of 50 to 60° C., which was predominantly methanol. The pressure was then lowered further to 5 mbar, and (R)-3-amino-1-butanol distilled over at a top temperature of 76° C. The product was distilled once again in a water jet pump vacuum, in the course of which (R)-3-amino-1-butanol distilled over at 93° C. and 26 mbar. This gave 125 g (91% of theory) of (R)-3-amino-1-butanol as a colorless liquid with an optical purity of 99.6% ee.

References

[1] TangXiao-Ling. "Efficient biosynthesis of (R)-3-amino-1-butanol by a novel (R)-selective transaminase from Actinobacteria sp." Journal of biotechnology 295 (2019): 49–54.
[2] HhneMatthias. "Rational assignment of key motifs for function guides in silico enzyme identification." Nature chemical biology 6 11 (2010): 807–13.