Reaktion #2186201

Reaktionsgleichung

3-Piperazin-1-yl-phenol

HCl

potassium carbonate

POCl3

→

2-hydroxy4-piperazin-1-yl-benzaldehyde

Lösungsmittel

EtOH

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigeslowly evaporated
2. 2
   SonstigeThe remaining beige powder is dried under high vacuum
3. 3
   workup.STIRRINGthe reaction mixture stirred for an hour at room temperature
4. 4
   Sonstige30 minutes
5. 5
   Sonstigeat 80° C.
6. 6
   workup.ADDITIONis added
7. 7
   workup.STIRRINGThe suspension is stirred 30 minutes at room temperature
8. 8
   Sonstigethen evaporated
9. 9
   workup.STIRRINGstirred in a 1:1 mixture of dichloromethane and isopropanol
10. 10
    FiltrationThe suspension is filtered
11. 11
    Sonstigethe filtrate evaporated
12. 12
    Sonstigedried

Vorschrift

890 mg (5 mmol) 3-Piperazin-1-yl-phenol are suspended in 100 mL EtOH and treated with 0.42 mL (1 eq.) 12N HCl at a temperature below 10° C. The suspension is stirred an hour and slowly evaporated. The remaining beige powder is dried under high vacuum, then taken up in 60 mL DMF. The solution is cooled to 5° C. under argon, 0.503 mL (1.1 eq.) POCl3 added dropwise and the reaction mixture stirred for an hour at room temperature, then 30 minutes at 80° C., and finally allowed to cool to room temperature, upon which 2 g (3 eq.) solid potassium carbonate is added. The suspension is stirred 30 minutes at room temperature then evaporated, and the residue resuspended and stirred in a 1:1 mixture of dichloromethane and isopropanol. The suspension is filtered, the filtrate evaporated and dried to yield 600 mg crude 2-hydroxy4-piperazin-1-yl-benzaldehyde. This material is taken up in 40 mL of a 1:1 mixture of benzene and acetonitrile, 2.5 mL (5 eq.) piperidine and 683 mg (0.66 eq.) benzothiazol-2-yl-acetic acid methyl ester are added under argon and the reaction mixture refluxed for an hour. The product is extracted with dichloromethane and brine at 0° C., the combined organic phases dried with sodium sulphate, filtered and evaporated, then triturated with diisopropylether to yield 800 mg desired product (crude).

Quelle