Hydrochloric Acid → (1,4-Dioxan-2-ylmethyl)methylamine hydrochloride

A solution of tosylate 22B-2 (7.76 kg), methylamine in ethanol (62 L of a 33 wt % solution) and ethanol (62 L) was heated to an internal temperature of 65° C. for 20 h. The resulting solution was then concentrated via atmospheric distillation to a volume of ˜15 L. This solution was held at 50° C. while NaOEt (9.2 L of a 21 wt % solution in ethanol; 1.05 equiv) was added, along with MTBE (47 L) each in two alternating portions. The slurry was then cooled to room temperature and filtered to remove sodium tosylate. The solids were washed with MTBE (15.5 L). The combined filtrates were solvent switched to isopropanol via atmospheric distillation. The final volume was ˜30 L. Conc. HCl (2.1 L of S.G. 1.18, 1.05 equiv) was added whilst keeping the temperature <60° C. Isopropanol (116 L) was added, and the batch was concentrated via atmospheric distillation to a total volume of ˜30 L. This mixture was held at 50° C. until a slurry formed, then cooled to room temperature overnight. The solids were filtered, washed with 1:1 heptane:isopropanol (15 L) and dried to give 22B-3 as a white solid. 1H NMR (400 MHz, MeOD): δ 3.90 (m, 2H), 3.77 (m, 3H), 3.62 (tr d, J=12 Hz, J=2.5 Hz, 1H), 3.36 (m, 1H), 3.06 (m, 2H), 2.73 (s, 3H)

1. concentrationThe resulting solution was then concentrated via atmospheric distillation to a volume of ˜15 L
2. customwas held at 50° C. while NaOEt
3. addition1.05 equiv) was added, along with MTBE (47 L) each in two alternating portions
4. filtrationfiltered
5. customto remove sodium tosylate
6. washThe solids were washed with MTBE (15.5 L)
7. distillationswitched to isopropanol via atmospheric distillation
8. customthe temperature <60° C
9. concentrationthe batch was concentrated via atmospheric distillation to a total volume of ˜30 L
10. customwas held at 50° C. until a slurry
11. customformed
12. temperaturecooled to room temperature overnight
13. filtrationThe solids were filtered
14. washwashed with 1:1 heptane
15. dry with materialisopropanol (15 L) and dried
16. customto give 22B-3 as a white solid

ORD 기록

ord-fd59f3281094464082260b30b6e6d1d6

출처 데이터셋

uspto-grants-2012_06

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08207186B2