Nalmefene hydrochloride → Nalmefene hydrochloride dihydrate

HRID 406936Notes

Reaction equation

HRID 406936 reaction equation
[CH2:1]=[C:2]1[C@@H:15]2[O:16][C:12]3[C:13]4[C@:14]52[CH2:17][CH2:18][N:19]([CH2:20][CH:21]2[CH2:23][CH2:22]2)[C@H:6]([CH2:7][C:8]=4[CH:9]=[CH:10][C:11]=3[OH:24])[C@:5]5([OH:25])[CH2:4][CH2:3]1.[ClH:26]>O>[CH2:1]=[C:2]1[C@@H:15]2[O:16][C:12]3=[C:11]([OH:24])[CH:10]=[CH:9][C:8]4=[C:13]3[C@:14]32[CH2:17][CH2:18][N:19]([CH2:20][CH:21]2[CH2:22][CH2:23]2)[C@H:6]([CH2:7]4)[C@:5]3([OH:25])[CH2:4][CH2:3]1.[OH2:16].[OH2:16].[ClH:26]

Participants

3

Reactant 1

HCID 5388881Nalmefene hydrochloride

Product 1

HCID 46209574Nalmefene hydrochloride dihydrateYield 192.7%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

Crude Nalmefene hydrochloride (7.67 Kg, assay 93.9%) and water (8.6 liter) were charged into a suitable reactor. The suspension was heated up to 80° C. until the substrate completely dissolved. Vacuum was then applied to remove organic solvents. The resulting solution was then filtered through a 0.65 μm cartridge and then diluted with water (2.1 liter) used to rinse the reactor and pipelines. The solution was cooled down to 50° C. and 7 g of Nalmefene hydrochloride dihydrate seeding material was added. The mixture was cooled down to 0-5° C. in one hour under efficient stirring and then maintained under stirring for one additional hour. The solid was filtered and washed with acetone. The wet product was dried at 25° C. under vacuum to provide Nalmefene hydrochloride dihydrate (5.4 Kg; yield 73%) with a chemical purity of 99.89% (HPLC).

Workup

  1. dissolutioncompletely dissolved
  2. customto remove organic solvents
  3. filtrationThe resulting solution was then filtered through a 0.65 μm cartridge
  4. additiondiluted with water (2.1 liter)
  5. washto rinse the reactor and pipelines
  6. temperatureThe solution was cooled down to 50° C.
  7. addition7 g of Nalmefene hydrochloride dihydrate seeding material was added
  8. temperatureThe mixture was cooled down to 0-5° C. in one hour
  9. temperaturemaintained
  10. stirringunder stirring for one additional hour
  11. filtrationThe solid was filtered
  12. washwashed with acetone
  13. customThe wet product was dried at 25° C. under vacuum

Sources & evidence

ORD record
ord-f93c3ae66c77405d83740c1b70b5215f
Source dataset
uspto-grants-2014_06
Patent number
US08754217B2

Reaction notes

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