Methanol → Leucine methyl ester hydrochloride

To a suspension of (L)-leucine, (315 g, 2.4 mol) in MeOH (3.2 L) at −15° C. was added SOCl2 (315 mL, 4.32 mol, 1.8 equiv.) dropwise at such a rate that the temp. of the reaction did not exceed 5° C. After the addition was complete, the reaction mixture was allowed to warm to room temp. and was stirred overnight. The resulting mixture was concentrated under reduced pressure and Et2O (3 L) was slowly added to the residue to produce a precipitate. The mixture was cooled with an ice bath, then treated with additional MeOH (3 L) relatively rapidly. After 1 h at 0° C., the crystals were collected and dried to give (L)-leucine methyl ester HCl salt as a white crystalline solid (394 g, 86%): mp 147-149° C.; 1H-NMR (CD3OD) δ0.78-0.98 (m, 6 h), 1.58-1.72 (m, 3H), 3.76 (g, 3H), 3.92 (t, J=7.3 Hz, 1H).

1. customdid not exceed 5° C
2. additionAfter the addition
3. temperatureto warm to room temp.
4. concentrationThe resulting mixture was concentrated under reduced pressure and Et2O (3 L)
5. additionwas slowly added to the residue
6. customto produce a precipitate
7. temperatureThe mixture was cooled with an ice bath
8. waitAfter 1 h at 0° C.
9. customthe crystals were collected
10. customdried

ORD record

ord-1e61807dc0d84b88ad8238f010ba58d6

Source dataset

uspto-grants-2002_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06353006B1