Hydrochloric Acid → (3R,4R,5R)-3-Amino-4,5-dimethyl-octanoic Acid Hydrochloride

Under nitrogen, 167 g of crude (3R,4R,5R)-3-acetylamino-4,5-dimethyl-octanoic acid ethyl ester was diluted 1100 mL of 6N HCl, stirred at room temperature for 16 hours, and then heated to reflux for another 24 hours. The reaction mixture was concentrated and recharged with 500 mL of isopropyl alcohol (IPA), which was subsequently removed. Acetonitrile (500 mL) was added to the crude white HCl salt and the mixture stirred at 20° C. to 25° C. for 1 hour. The resulting slurry was filtered, and the solids isolated to give 97 g of the titled compound (67% yield, 89.7% chemical purity; 90.7% chiral purity with two major diastereomers, 6.8% and 1.5%): 1H NMR (CD3OD): δ 0.89t J=7.0 Hz, 3H), 0.94t, J=6.9 Hz, 6H), 1.65–1.0 (m, 4H), 2.61 (dd, J=7.6 Hz, 1H), 2.73 (dd, J=4.6 HZ, 1H), 3.27 (m, J=1.6 Hz, 2H), 3.56 (m, 1H), 4.82 (s, 3H).

1. temperatureheated
2. temperatureto reflux for another 24 hours
3. concentrationThe reaction mixture was concentrated
4. customwas subsequently removed
5. additionAcetonitrile (500 mL) was added to the crude white HCl salt
6. stirringthe mixture stirred at 20° C. to 25° C. for 1 hour
7. filtrationThe resulting slurry was filtered
8. customthe solids isolated

ORD record

ord-a3917dcb73bd4fb0b38d36b3b925e731

Source dataset

uspto-grants-2007_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07179934B2