Thionyl Chloride → N-(1S)-(1-(chloromethyl)-3-methylbutyl)-N-(isobutyl)amine HCl salt

Temperature

90 °C

To a solution of (2S)-4-methyl-2-(isobutylamino)pentan-1-ol (Method B4c; 256 g, 1.5 mol) and toluene (2.5 L) was added SOCl2 (167 mL) over 15 min. After the addition of SOCl2 was complete the reaction was heated at 90° C. overnight. The reaction solution was then cooled to room temp. and concentrated under reduced pressure. The dark oily residue was dissolved in CH2Cl2 (2 L) and concentrated under reduced pressure. The red-brown residue was dissolved in Et2O (1 L), and hexane (750 mL) was added dropwise over a period of 8 h. The resulting slurry was stirred overnight, filtered, and washed with a 40% EtOAc/hex solution to give N-(1S)-(1-(chloromethyl)-3-methylbutyl)-N-(isobutyl)amine HCl salt as a dark brown solid (276 g): 1H NMR (CDCl3) δ0.93-1.00 (m, 6H), 1.10-1.12 (m, 6H), 1.85 (m, 4H), 2.24-2.34 (m, 2H), 2.80-2.88 (m, 1H), 2.90-3.02 (m, 1H), 3.50-3.57 (m, 1H), 3.96 (dd, J=12.9, 5.6 Hz, 1H), 4.10 (dd, J=13.2, 3.6 Hz, 1H).

1. temperatureThe reaction solution was then cooled to room temp.
2. concentrationconcentrated under reduced pressure
3. dissolutionThe dark oily residue was dissolved in CH2Cl2 (2 L)
4. concentrationconcentrated under reduced pressure
5. dissolutionThe red-brown residue was dissolved in Et2O (1 L)
6. additionhexane (750 mL) was added dropwise over a period of 8 h
7. filtrationfiltered
8. washwashed with a 40% EtOAc/hex solution

ORD record

ord-2980885bd695465ba5c6cc0ec5da0e5d

Source dataset

uspto-grants-2002_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06353006B1