Nitrogen → HCID 69672148, compound

In a flame dried round-bottomed flask equipped with a magnetic stir bar and under inert atmosphere (N2), to a solution of 2,2-difluoro-1-(pyrrolidin-1-yl)pent-4-en-1-one (260 mg, 1.37 mmol) in dry THF (15 mL) was added BH3-THF (6.6 mL of a 1M solution in THF, 6.60 mmol) at rt. The reaction mixture was stirred at reflux for 18 h, cooled down to rt and concentrated under reduced pressure. The residue was redissolved in MeOH (slow addition) and concentrated under reduced pressure (2×). The resulting oil was then redissolved in THF (5 mL), treated with aq. 2N NaOH (0.8 mL) and aq. 30% H2O2 (0.8 mL). The mixture was stirred at rt for 2 h. Water was then added, the layers separated and the aq. layer extracted with EA. The combined org. extracts were washed with brine, dried (MgSO4), filtered and concentrated under reduced pressure. The crude residue was purified by FC (hept-EA, 1:1→3:7) to give 4,4-difluoro-5-(pyrrolidin-1-yl)pentan-2-ol as a colorless oil and 4,4-difluoro-5-(pyrrolidin-1-yl)pentan-1-ol as a yellow oil. LC-MS-conditions 08: tR=0.38 min; [M+H]+=194.39 and tR=0.51 min; [M+H]+=194.38.

1. temperatureat reflux for 18 h
2. concentrationconcentrated under reduced pressure
3. dissolutionThe residue was redissolved in MeOH (slow addition)
4. concentrationconcentrated under reduced pressure (2×)
5. dissolutionThe resulting oil was then redissolved in THF (5 mL)
6. additiontreated with aq. 2N NaOH (0.8 mL) and aq. 30% H2O2 (0.8 mL)
7. stirringThe mixture was stirred at rt for 2 h
8. additionWater was then added
9. customthe layers separated
10. extractionthe aq. layer extracted with EA
11. washextracts were washed with brine
12. dry with materialdried (MgSO4)
13. filtrationfiltered
14. concentrationconcentrated under reduced pressure
15. customThe crude residue was purified by FC (hept-EA, 1:1→3:7)

ORD record

ord-b78d1f077cf74cee8e1fcc596f691feb

Source dataset

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09187435B2