Diisobutylaluminum hydride → HCID 89544619, compound

Temperature

-10 °C

1-(3,5-Difluoro-4-pyridyl)cyclopropanecarbonitrile (3.74 g, 20.8 mmol) was dissolved in Toluene (69.2 mL). At −10° C. DIBAL-H in Toluene 1.0M (43.6 mL, 43.6 mmol) was added dropwise to the yellow solution. The reaction mixture was stirred 30 min at −10° C. The mixture was then cooled down to −65° C. At −65° C. NaBH4 (4.81 g, 125 mmol) was added, then carefully 50 mL MeOH. The reaction mixture was stirred 1 h at −50° C., after approximately 30 min a sudden and strong gas evolution occurred and the temperature rose to −30° C. The reaction mixture was poured into 200 mL of 1M potassium sodium tartrate. The pale yellow solution was extracted 3 times with Ether. The combined organic phases were washed with brine and dried with Na2SO4, filtrated and the filtrate evaporated that gave a colorless mixture of oil and solid (3.95 g). The residue was dissolved in Ether and extracted with 4N HCl. The water layer was put to pH=10 with NaOH 30% in water until a white suspension appeared. The suspension was filtrated and washed with ether. The water layer from the filtrate was extracted 3 times with ether. The combined organic layers were dried with Na2SO4, filtrated and evaporated. The residue was a colorless mixture of oil and solid. The mixture was triturated with Ether and the solid was filtrated, the filtrate evaporated which gave the desired product as colorless oil (1.383 g).

1. customAt −10° C
2. temperatureThe mixture was then cooled down to −65° C
3. customAt −65° C
4. stirringThe reaction mixture was stirred 1 h at −50° C., after approximately 30 min a sudden and strong gas evolution
5. customrose to −30° C
6. extractionThe pale yellow solution was extracted 3 times with Ether
7. washThe combined organic phases were washed with brine
8. dry with materialdried with Na2SO4
9. filtrationfiltrated
10. customthe filtrate evaporated
11. customthat gave
12. extractionextracted with 4N HCl
13. filtrationThe suspension was filtrated
14. washwashed with ether
15. extractionThe water layer from the filtrate was extracted 3 times with ether
16. dry with materialThe combined organic layers were dried with Na2SO4
17. filtrationfiltrated
18. customevaporated
19. additiona colorless mixture of oil and solid
20. customThe mixture was triturated with Ether
21. filtrationthe solid was filtrated
22. customthe filtrate evaporated which

ORD record

ord-4810c77523194f23a8e18f5050b0bb66

Source dataset

uspto-grants-2015_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09040708B2