Dimethylamine → Rocastine fumarate

HRID 1194220Notes

Reaction equation

HRID 1194220 reaction equation
[CH3:1][NH:2][CH3:3].C(O)C.Cl[CH2:8][CH2:9][CH:10]1[CH2:16][N:15]([CH3:17])[C:14](=[S:18])[C:13]2[CH:19]=[CH:20][CH:21]=[N:22][C:12]=2[O:11]1.[C:23]([OH:30])(=[O:29])/[CH:24]=[CH:25]/[C:26]([OH:28])=[O:27]>C(Cl)Cl.C(O)(C)C.CO>[C:23]([OH:30])(=[O:29])/[CH:24]=[CH:25]/[C:26]([OH:28])=[O:27].[CH3:1][N:2]([CH3:3])[CH2:8][CH2:9][CH:10]1[CH2:16][N:15]([CH3:17])[C:14](=[S:18])[C:13]2[CH:19]=[CH:20][CH:21]=[N:22][C:12]=2[O:11]1

Participants

8

Reactant 4

HCID 674DimethylamineHCID 702EthanolHCID 444972Fumaric AcidHCID 137264422-(chloroethyl)-2,3-dihydro-4-methylpyrido[3,2-f]-1,4-oxazepine-5(4H)thione

Product 1

HCID 6917885Rocastine fumarate

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 3776IsopropanolSolvent2×HCID 6344DichloromethaneSolvent

Procedure

To a solution of 113 ml (1.0 mole) of 40% aqueous dimethylamine and 326 ml of ethanol in a steel bomb was added 48.4 g (0.189 mole) of 2-(2-chloroethyl)-2,3-dihydro-4-methylpyrido[3,2-f][1,4]-oxazepine-5(4H)-thione. The mixture was heate at 100° C. for 14 hr. The ethanol was removed in a rotary evaporator leaving some water in the residue. The residue was dissolved in 200 ml of methylene chloride and washed with three 100 ml portions of 20% aqueous potassium carbonate solution. The combined aqueous layers were extracted with three 150 ml portions of methylene chloride. Methylene chloride solutions were combined and treated with charcoal. Charcoal was filtered off and the filtrate was evaporated to give an oil. The oil was dissolved in 215 ml isopropyl alcohol and the solution was heated to a slow boil. A solution of 21.9 g (0.19 mole) of fumaric acid in 150 ml of boiling methanol was added to the isopropyl alcohol solution. Crystalline solid was obtained weighing 63.4 g (88%). The solid was recrystallized from hot 200 proof ethyl alcohol. The crystals were filtered off and triturated in isopropyl ether at room temperature and again separated by filtering. After drying in a vacuum oven overnight at 85° C., crystals in the amount of 72.45 g (79%), m.p. 130°-133° C., were obtained.

Workup

  1. customat 100° C.
  2. customfor 14 hr
  3. customThe ethanol was removed in a rotary evaporator
  4. customleaving some water in the residue
  5. washwashed with three 100 ml portions of 20% aqueous potassium carbonate solution
  6. extractionThe combined aqueous layers were extracted with three 150 ml portions of methylene chloride
  7. additiontreated with charcoal
  8. filtrationCharcoal was filtered off
  9. customthe filtrate was evaporated
  10. customto give an oil
  11. temperaturethe solution was heated to a slow boil
  12. customCrystalline solid was obtained
  13. customThe solid was recrystallized from hot 200 proof ethyl alcohol
  14. filtrationThe crystals were filtered off
  15. customtriturated in isopropyl ether at room temperature
  16. customagain separated
  17. filtrationby filtering
  18. customAfter drying in a vacuum oven overnight at 85° C.
  19. customcrystals in the amount of 72.45 g (79%), m.p. 130°-133° C., were obtained

Sources & evidence

ORD record
ord-e1bdf4cc55fb4a83a6186f23e0310f47
Source dataset
uspto-grants-1989_03
Patent number
US04812565

Reaction notes

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