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

HRID 1366351Notes

Reaction equation

HRID 1366351 reaction equation
S(C1C=CC(C)=CC=1)([O-])(=O)=O.[CH3:12][NH2:13].[ClH:14].[CH:15]([OH:18])([CH3:17])[CH3:16].[CH2:19]([OH:21])[CH3:20]>>[ClH:14].[O:18]1[CH2:20][CH2:19][O:21][CH2:16][CH:15]1[CH2:17][NH:13][CH3:12]

Participants

6

Reactant 5

HCID 313Hydrochloric AcidHCID 702Ethanol2×HCID 3776IsopropanolHCID 6329MethylamineHCID 85570p-Toluenesulfonate

Product 1

HCID 66972118(1,4-Dioxan-2-ylmethyl)methylamine hydrochloride

Procedure

A solution of tosylate 1B-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 1B-3 as a white solid.

Workup

  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 1B-3 as a white solid

Sources & evidence

ORD record
ord-b3b1c13ae7cd4cdb801f163fb529125f
Source dataset
uspto-grants-2011_02
Patent number
US07893081B2

Reaction notes

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