4-Formylbenzoic acid → 4-(4-Cyclopropyl-piperazine-1-carbonyl)-benzaldehyde

Temperature

60 °C

A mixture of 4-formyl-benzoic acid (54.4 g), toluene (500 mL), DMF (3.6 mL), and thionyl chloride (30.4 mL) was heated at 60° C. for 2 h and then was cooled to 5° C. In a separate flask, a 5° C. mixture of NaOH (50.7 g), water (550 mL), and toluene (150 mL) was treated with 1-cyclopropyl-piperazine dihydrochloride (70.0 g) in portions while the temperature was maintained below 10° C. After the addition was complete, the mixture was cooled to 5° C. and treated with the crude acyl chloride solution prepared as above at a rate such that the temperature did not exceed 10° C. After the addition was complete, the mixture was allowed to warm to room temperature and was stirred overnight. The biphasic mixture was basified to pH˜10 with 1 N NaOH (300 mL). The layers were separated and the aqueous layer was extracted with toluene (100 mL×2). The combined organic layers were washed with brine (200 mL), dried (Na2SO4), and concentrated to yield the title compound as pale yellow viscous oil.

1. temperaturewas cooled to 5° C
2. temperaturewas maintained below 10° C
3. additionAfter the addition
4. temperaturethe mixture was cooled to 5° C.
5. customdid not exceed 10° C
6. additionAfter the addition
7. temperatureto warm to room temperature
8. customThe layers were separated
9. extractionthe aqueous layer was extracted with toluene (100 mL×2)
10. washThe combined organic layers were washed with brine (200 mL)
11. dry with materialdried (Na2SO4)
12. concentrationconcentrated

ORD record

ord-be442297000b4de8aed646cb56a21c0e

Source dataset

uspto-grants-2010_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07728129B2