Hydrochloric Acid → 2-Hydroxy4-piperazin-1-yl-benzaldehyde

Temperature

5 °C

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).

1. customslowly evaporated
2. customThe remaining beige powder is dried under high vacuum
3. stirringthe reaction mixture stirred for an hour at room temperature
4. custom30 minutes
5. customat 80° C.
6. additionis added
7. stirringThe suspension is stirred 30 minutes at room temperature
8. customthen evaporated
9. stirringstirred in a 1:1 mixture of dichloromethane and isopropanol
10. filtrationThe suspension is filtered
11. customthe filtrate evaporated
12. customdried

ORD record

ord-d8f104cc5ae444a0b7efee0be703425c

Source dataset

uspto-grants-2009_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07569337B2