4-Chlorophenol → 3-(4-Chlorophenoxy)pyrrolidine

Temperature

0 °C

3-Hydroxy-pyrrolidine-1-carboxylic acid tert butyl ester (2.1 g, 9.9 mmol) and triphenyl phosphine (2.59 g, 9.9 mmol) were dissolved in dry THF (35 ml) under nitrogen. The solution was cooled to 0° C. and 4-chlorophenol (1.28 g, 9.9 mmol) dissolved in dry THF (10 ml) was added followed by diethyl azodicarboxylate (DEAD) (1.55 ml, 9.9 mmol). After 15 minutes the ice bath was removed and the reaction was stirred overnight. The reaction mixture was concentrated under reduced pressure and the residue was stirred with ether. The solid triphenyl phosphine oxide was filtered off. The solution was washed three times with sodium hydroxide (1M) and concentrated. The BOC-protected product was purified by flash chromatography on silica using EtOAc/heptane as eluant. It was dissolved in dichloromethane (35 ml) and trifluoroacetic acid (17 ml). The reaction mixture was stirred at room temperature overnight, concentrated and purified by flash chromatography on silica (MeOH:CHCl3:NH3, 100:100:1) to give the subtitle compound (1.72 g, 88%).

1. additionwas added
2. customAfter 15 minutes the ice bath was removed
3. concentrationThe reaction mixture was concentrated under reduced pressure
4. stirringthe residue was stirred with ether
5. filtrationThe solid triphenyl phosphine oxide was filtered off
6. washThe solution was washed three times with sodium hydroxide (1M)
7. concentrationconcentrated
8. customwas purified by flash chromatography on silica
9. dissolutionIt was dissolved in dichloromethane (35 ml)
10. stirringThe reaction mixture was stirred at room temperature overnight
11. concentrationconcentrated
12. custompurified by flash chromatography on silica (MeOH:CHCl3:NH3, 100:100:1)

ORD record

ord-4c62a3c0a8eb4006b169d178063a1876

Source dataset

uspto-grants-2005_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06951874B2