Nitrogen → (3R)-3-Fluoro-1-pyrrolidinebutanamine

In a flame dried round-bottomed flask equipped with a magnetic stir bar and under inert atmosphere (N2), to a solution of (R)-3-fluoropyrrolidine hydrochloride (400 mg, 3.09 mmol) and 4-bromobutyronitrile (0.32 mL, 3.09 mmol) in dry CH3CN (16 mL) was added K2CO3 (2.35 g, 16.99 mmol) at rt followed by KI (51 mg, 0.31 mmol). The reaction mixture was stirred at rt for 15 h. The mixture was filtered and the filtrate partitioned between water and CH2Cl2. The layers were separated and the aq. layer extracted with CH2Cl2 (3×). The combined org. extracts were dried over MgSO4, filtered and concentrated under reduced pressure. The crude nitrile was redissolved in dry THF (23 mL) and treated with LiALH4 (214 mg, 5.47 mmol) at 0° C. The reaction mixture was warmed up to rt and stirred at this temperature until completion of the reaction. Aq. 1N NaOH (7 mL) was then added, the layers separated and the aq. layer extracted with EA (3×). The combined organic extracts were washed with brine, dried over Na2SO4, filtered, and the solvents were removed under reduced pressure to give crude (R)-4-(3-fluoropyrrolidin-1-yl)butan-1-amine as a colorless oil. GC-MS-conditions 01: tR=1.71 min; [M+H]+=161.10.

1. filtrationThe mixture was filtered
2. customthe filtrate partitioned between water and CH2Cl2
3. customThe layers were separated
4. extractionthe aq. layer extracted with CH2Cl2 (3×)
5. dry with materialextracts were dried over MgSO4
6. filtrationfiltered
7. concentrationconcentrated under reduced pressure
8. dissolutionThe crude nitrile was redissolved in dry THF (23 mL)
9. additiontreated with LiALH4 (214 mg, 5.47 mmol) at 0° C
10. temperatureThe reaction mixture was warmed up to rt
11. stirringstirred at this temperature until completion of the reaction
12. additionAq. 1N NaOH (7 mL) was then added
13. customthe layers separated
14. extractionthe aq. layer extracted with EA (3×)
15. washThe combined organic extracts were washed with brine
16. dry with materialdried over Na2SO4
17. filtrationfiltered
18. customthe solvents were removed under reduced pressure

ORD record

ord-7d74f3516291478c9645b54471bfad42

Source dataset

uspto-grants-2013_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08563714B2