Reaction #1135856

Reaction equation

Choline hydroxide

diazoxide

choline hydroxide

→

diazoxide choline

Solvents

THF

Conditions

Workup

1. 1
   workup.STIRRINGwith stirring
2. 2
   TemperatureThe temperature was maintained at 60±5° C
3. 3
   workup.STIRRINGstirring
4. 4
   FiltrationThe reaction mixture was clarified by in-line 10 micron filtration upon transfer to a 22-L reaction flask
5. 5
   workup.ADDITIONpre-charged with 2-L
6. 6
   Filtrationpre-filtered THF
7. 7
   workup.ADDITIONinto which was added 10-L
8. 8
   Filtrationpre-filtered MTBE dropwise
9. 9
   OtherThis reaction mixture was transferred to another flask
10. 10
    workup.ADDITIONwhich was then charged with an additional 30-L
11. 11
    Filtrationpre-filtered MTBE dropwise
12. 12
    workup.STIRRINGwith adjustment of temperature to <5° C. and stirring for about 2 hr
13. 13
    FiltrationDiazoxide choline salt was recovered by vacuum filtration

Procedure

A 12-L reaction flash was charged with 2.0 kg diazoxide and 5.0-L THF with stirring and heating to 55° C. Choline hydroxide (45% solution in methanol, 2.32 L) was added dropwise to this reaction mixture over about 2.5 hr with stirring. The temperature was maintained at 60±5° C. After addition of choline hydroxide, stirring was continued for about 30 min. The reaction mixture was clarified by in-line 10 micron filtration upon transfer to a 22-L reaction flask pre-charged with 2-L pre-filtered THF, into which was added 10-L pre-filtered MTBE dropwise. This reaction mixture was transferred to another flask which was then charged with an additional 30-L pre-filtered MTBE dropwise, with adjustment of temperature to <5° C. and stirring for about 2 hr. Diazoxide choline salt was recovered by vacuum filtration to afford 2.724 kg (94%) diazoxide choline salt (99.8%, HPLC purity), confirmed by 1H NMR, IR, and UV/Visible analysis.

Source